SQSTM1

Summary

Gene Symbol: SQSTM1
Description: sequestosome 1
Alias: A170, DMRV, FTDALS3, NADGP, OSIL, PDB3, ZIP3, p60, p62, p62B, sequestosome-1, EBI3-associated protein of 60 kDa, EBI3-associated protein p60, EBIAP, oxidative stress induced like, phosphotyrosine independent ligand for the Lck SH2 domain p62, phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa, ubiquitin-binding protein p62
Species: human

Top Publications

  1. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
  2. pmc SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis
    Isabelle Le Ber
    INSERM, UMR_S975, Centre de Recherche de l Institut du Cerveau et de la Moelle Epiniere, Hopital de la Salpetriere, F 75013, Paris, France2Université Pierre Marie Curie Paris 06, UMR_S975, F 75013, Paris, France3Centre national de la recherche scientifique, UMR 7225, F 75013, Paris, France4AP HP, Hopital de la Pitie Salpetriere, Centre de Référence des Démences Rares, Paris, France5AP HP, Hopital de la Pitie Salpetriere, Département des Maladies du Système Nerveux, Paris, France
    JAMA Neurol 70:1403-10. 2013
  3. doi Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage
    Soo Han Bae
    Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120 750, Korea
    Cell Metab 17:73-84. 2013
  4. pmc SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Elisa Rubino
    Neurology II, Department of Internal Medicine, University of Torino, Torino, Italy
    Neurology 79:1556-62. 2012
  5. pmc A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes
    O Devergne
    Department of Microbiology and Molecular Genetics, Harvard University, Boston, Massachusetts, USA
    J Virol 70:1143-53. 1996
  6. doi Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology
    Elisa Teyssou
    Inserm UMR_S975, CNRS UMR7225, Université Pierre et Marie Curie Sorbonne Universités, Hopital Pitie Salpetriere, Paris, France
    Acta Neuropathol 125:511-22. 2013
  7. doi Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation
    Chan Gao
    The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China
    Nat Cell Biol 12:781-90. 2010
  8. doi Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1 signaling
    Kohsuke Yamazaki
    Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
    Sci Signal 2:ra66. 2009
  9. doi Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis
    Makito Hirano
    Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan
    Neurology 80:458-63. 2013
  10. ncbi Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B
    Vidya Mamidipudi
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 277:28010-8. 2002

Research Grants

  1. Mechanisms of Ubiquitin Trafficking in Neurons
    Michael C Wooten; Fiscal Year: 2013
  2. Role of p62 in Protein Aggregation and Neurodegeneration in ALS
    Haining Zhu; Fiscal Year: 2009
  3. Arunabh Bhattacharya; Fiscal Year: 2014
  4. Junichi Sadoshima; Fiscal Year: 2014
  5. Molecular mechanism underlying Frontotemporal Lobar Regeneration
    David Medina; Fiscal Year: 2013
  6. Wei Xing Zong; Fiscal Year: 2016
  7. Autophagy and human islet amyloid polypeptide in animal models of type 2 diabetes
    Jacqueline Rivera; Fiscal Year: 2013
  8. Meiosis, SUMOylation and the ZIP3 Protein: Parallel Studies in Mouse and Yeast.
    Neil Hunter; Fiscal Year: 2012
  9. Stephen B Howell; Fiscal Year: 2014
  10. Steven M Lipkin; Fiscal Year: 2015

Detail Information

Publications255 found, 100 shown here

  1. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
    ..The polyubiquitin-binding protein p62/SQSTM1 is degraded by autophagy...
  2. pmc SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis
    Isabelle Le Ber
    INSERM, UMR_S975, Centre de Recherche de l Institut du Cerveau et de la Moelle Epiniere, Hopital de la Salpetriere, F 75013, Paris, France2Université Pierre Marie Curie Paris 06, UMR_S975, F 75013, Paris, France3Centre national de la recherche scientifique, UMR 7225, F 75013, Paris, France4AP HP, Hopital de la Pitie Salpetriere, Centre de Référence des Démences Rares, Paris, France5AP HP, Hopital de la Pitie Salpetriere, Département des Maladies du Système Nerveux, Paris, France
    JAMA Neurol 70:1403-10. 2013
    Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS)...
  3. doi Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage
    Soo Han Bae
    Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120 750, Korea
    Cell Metab 17:73-84. 2013
    ..We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the antioxidant function of Sesns is mediated through activation of Nrf2 in ..
  4. pmc SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Elisa Rubino
    Neurology II, Department of Internal Medicine, University of Torino, Torino, Italy
    Neurology 79:1556-62. 2012
    ..Recently, mutations in the sequestosome 1 (SQSTM1) gene, which encodes p62 protein, have been reported in patients with ALS...
  5. pmc A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes
    O Devergne
    Department of Microbiology and Molecular Genetics, Harvard University, Boston, Massachusetts, USA
    J Virol 70:1143-53. 1996
    ..EBI3 synthesis by trophoblasts and by EBV-transformed cells and similarities to interleukin-12 p40 are compatible with a role for EBI3 in regulating cell-mediated immune responses...
  6. doi Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology
    Elisa Teyssou
    Inserm UMR_S975, CNRS UMR7225, Université Pierre et Marie Curie Sorbonne Universités, Hopital Pitie Salpetriere, Paris, France
    Acta Neuropathol 125:511-22. 2013
    Mutations in SQSTM1 encoding the sequestosome 1/p62 protein have recently been identified in familial and sporadic cases of amyotrophic lateral sclerosis (ALS)...
  7. doi Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation
    Chan Gao
    The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China
    Nat Cell Biol 12:781-90. 2010
    ..Von Hippel-Lindau protein-mediated ubiquitylation is critical for the binding of Dvl2 to p62, which in turn facilitates the aggregation and the LC3-mediated autophagosome recruitment of Dvl2 under starvation; ..
  8. doi Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1 signaling
    Kohsuke Yamazaki
    Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
    Sci Signal 2:ra66. 2009
    ..Therefore, we propose that the cooperative activation of NF-kappaB by two mechanistically and temporally distinct MEKK3-dependent pathways that diverge at TRAF6 critically contributes to immune and inflammatory systems...
  9. doi Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis
    Makito Hirano
    Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan
    Neurology 80:458-63. 2013
    The purpose of this study was to find mutations in the SQSTM1 gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis (ALS), since this gene has been recently identified as a causative gene for familial and sporadic ALS ..
  10. ncbi Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B
    Vidya Mamidipudi
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 277:28010-8. 2002
    ..the p75-NGF receptor leading to formation of a complex between IRAK, atypical protein kinase C interacting protein, p62, and TRAF6...
  11. doi Sequestosome 1 mutations in Paget's disease of bone in Australia: prevalence, genotype/phenotype correlation, and a novel non-UBA domain mutation (P364S) associated with increased NF-kappaB signaling without loss of ubiquitin binding
    Sarah L Rea
    Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Nedlands, Australia
    J Bone Miner Res 24:1216-23. 2009
    Previously reported Sequestosome 1(SQSTM1)/p62 gene mutations associated with Paget's disease of bone (PDB) cluster in, or cause deletion of, the ubiquitin-associated (UBA) domain...
  12. pmc Inhibition of mTOR kinase by AZD8055 can antagonize chemotherapy-induced cell death through autophagy induction and down-regulation of p62/sequestosome 1
    Shengbing Huang
    Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota 55905, USA
    J Biol Chem 286:40002-12. 2011
    ..autophagy, as shown by LC3I-II conversion and down-regulation of the ubiquitin-binding protein p62/sequestosome 1. AZD8055-induced autophagy was pro-survival as shown by its ability to attenuate cell death and DNA damage (p-..
  13. pmc Sequestosome-1 (SQSTM1) sequence variants in ALS cases in the UK: prevalence and coexistence of SQSTM1 mutations in ALS kindred with PDB
    Chun T Kwok
    Neurogenetics Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
    Eur J Hum Genet 22:492-6. 2014
    Mutations in the SQSTM1 gene have been reported to be associated with amyotrophic lateral sclerosis (ALS). We sought to determine the frequency of these mutations in a UK familial ALS (FALS) cohort...
  14. ncbi The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor
    M W Wooten
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 276:7709-12. 2001
    ..Here we show that the atypical protein kinase C-interacting protein, p62, which binds TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts with p75 but not TrkA...
  15. pmc Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates
    Kathryn M Donaldson
    Department of Cancer and Cell Biology, Genomics Institute of the Novartis Research Foundation GNF, 10675 John J Hopkins Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 100:8892-7. 2003
    ..Both wild-type Atx-3 and the otherwise unrelated Ub-binding protein p62/Sequestosome-1 have been shown to be sequestered into aggregates in affected neurons in several neurodegenerative ..
  16. pmc Regulation of MyD88 aggregation and the MyD88-dependent signaling pathway by sequestosome 1 and histone deacetylase 6
    Takeshi Into
    Department of Oral Microbiology, Asahi University School of Dentistry, 1851 1 Hozumi, Mizuho, Gifu 501 0296, Japan
    J Biol Chem 285:35759-69. 2010
    ..In addition, formation of large aggregated structures is related to cytoplasmic accumulation of sequestosome 1 (SQSTM1; also known as p62) and histone deacetylase 6 (HDAC6), which are involved in accumulation of ..
  17. pmc p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
    Kei Okatsu
    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    Genes Cells 15:887-900. 2010
    ..In addition, p62/SQSTM1 (hereafter referred to as p62) was recruited to depolarized mitochondria after Parkin-directed ubiquitylation...
  18. pmc p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD, USA
    Autophagy 6:1090-106. 2010
    ..polyubiquitination of mitochondrial substrate(s) and recruits the ubiquitin- and LC3-binding protein, p62/SQSTM1, to mitochondria...
  19. ncbi Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations
    E W M Eekhoff
    Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Arthritis Rheum 50:1650-4. 2004
    To estimate the occurrence of familial Paget's disease of bone in The Netherlands, to examine the prevalence of mutations of the sequestosome 1 gene (SQSTM1) in identified families, and to assess potential genotype-phenotype associations.
  20. ncbi In vitro production of Mallory bodies and intracellular hyaline bodies: the central role of sequestosome 1/p62
    Conny Stumptner
    Institute of Pathology, Medical University of Graz, Graz, Austria
    Hepatology 46:851-60. 2007
    ..MBs and IHBs contain ubiquitin and sequestosome 1/p62 (p62), a stress-inducible adapter protein with affinity to polyubiquitinated proteins...
  21. doi Absence of somatic SQSTM1 mutations in Paget's disease of bone
    Brya G Matthews
    Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Clin Endocrinol Metab 94:691-4. 2009
    ..Mutations in the SQSTM1 gene are found in about one third of families with Paget's disease and 8% of sporadic cases...
  22. pmc Somatic mutations in SQSTM1 detected in affected tissues from patients with sporadic Paget's disease of bone
    Anand Merchant
    Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    J Bone Miner Res 24:484-94. 2009
    ..studies of familial PDB showed that a majority of cases harbor germline mutations in the Sequestosome1 gene (SQSTM1). In contrast, little is known about the mutational status of SQSTM1 in sporadic PDB...
  23. doi Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases
    Kunikazu Tanji
    Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
    J Neuropathol Exp Neurol 72:18-28. 2013
    ..One of the Nrf2 targets, p62, has been known to be incorporated into a wide spectrum of cytoplasmic inclusions in neurodegenerative diseases and ..
  24. doi Knockdown of p62/sequestosome 1 attenuates autophagy and inhibits colorectal cancer cell growth
    Feng Ren
    Department of Geriatrics Surgery, Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, China
    Mol Cell Biochem 385:95-102. 2014
    b>p62/sequestosome-1 is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis, and plays an important role at the crossroad between autophagy and cancer...
  25. pmc Insulin receptor substrate 1/2 (IRS1/2) regulates Wnt/β-catenin signaling through blocking autophagic degradation of dishevelled2
    Yongtao Geng
    From the School of Life Sciences, Peking University, Beijing 100871, China
    J Biol Chem 289:11230-41. 2014
    ..We further revealed that IRS1/2 blocks autophagy-induced formation of the Dvl2-p62/SQSTM1 complex, resulting in disabled association of Dvl2 to autophagosomes...
  26. doi SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis
    Faisal Fecto
    Division of Neuromuscular Medicine, Ken and Ruth Davee Department of Neurology and Clinical Neurological Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Arch Neurol 68:1440-6. 2011
    The SQSTM1 gene encodes p62, a major pathologic protein involved in neurodegeneration.
  27. ncbi p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins
    R K Vadlamudi
    Division of Tumor Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:20235-7. 1996
    b>p62 is a novel cellular protein which was initially identified as a phosphotyrosine-independent ligand of the SH2 domain of p56(lck). In the yeast two-hybrid system, p62 specifically interacted with ubiquitin in vivo...
  28. pmc The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Czeta
    Bertrand Cariou
    Departement d Endocrinologie, Institut Cochin, CNRS INSERM Université René Descartes 75674 Paris, France
    Mol Cell Biol 22:6959-70. 2002
    ..Together, these results suggest that Grb14, ZIP, and PKCzeta participate in a new feedback pathway of insulin signaling...
  29. doi The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes
    Elena Shvets
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Cell Sci 121:2685-95. 2008
    ..The N-terminal region was found to be important for interaction between LC3 and p62/SQSTM1 (hereafter termed p62)...
  30. ncbi Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB)
    Alberto Falchetti
    Department of Internal Medicine, Azienda Ospedaliera Careggi, Florence, Italy
    J Bone Miner Res 19:1013-7. 2004
    ..We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder...
  31. pmc Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62
    P Sanchez
    Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Universidad Autonoma, Canto Blanco, Spain
    Mol Cell Biol 18:3069-80. 1998
    ..Here we report the identification of p62, a previously described phosphotyrosine-independent p56(lck) SH2-interacting protein, as a molecule that interacts ..
  32. ncbi Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins
    Trond Lamark
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 278:34568-81. 2003
    ..Among the last group, p62 and Par6 (partitioning-defective 6) are involved in coupling the aPKCs to signaling pathways involved in cell ..
  33. pmc Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone
    Nancy Laurin
    Centre de recherche en endocrinologie moléculaire et oncologique, Centre de Recherche du Centre Hospitalier de l Universite Laval, 2705 Laurier Boulevard, Quebec, PQ, Canada G1V 4G2
    Am J Hum Genet 70:1582-8. 2002
    ..This region encoded the ubiquitin-binding protein sequestosome 1 (SQSTM1/p62), which is a candidate gene for PDB because of its association with the NF-kappaB pathway...
  34. pmc p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription
    Ashish Jain
    Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 285:22576-91. 2010
    The p62/SQSTM1 (sequestosome 1) protein, which acts as a cargo receptor for autophagic degradation of ubiquitinated targets, is up-regulated by various stressors...
  35. pmc TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS)
    Ken ichi Fujita
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD USA
    Autophagy 7:552-4. 2011
    ..in macrophages is selective autophagy of aggresome-like induced structures (ALIS), and p62 (also known as SQSTM1) plays an essential role in this process...
  36. doi p62/SQSTM1/A170: physiology and pathology
    Masaaki Komatsu
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    Pharmacol Res 66:457-62. 2012
    p62/SQSTM1/A170 (hereafter referred to as p62) is a stress-inducible intracellular protein known to regulate various signal transduction pathways involved in cell survival and cell death...
  37. pmc The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation
    L Sanz
    Laboratorio Glaxo Wellcome CSIC de Biología Molecular y Celular, Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Spain
    EMBO J 18:3044-53. 1999
    ..Here we show that the previously described aPKC-binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo...
  38. pmc p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases
    Kurt Zatloukal
    Department of Pathology, Karl Franzens University, Graz, Austria
    Am J Pathol 160:255-63. 2002
    ..Using 2D gel electrophoresis and mass spectrometry, we identified p62 as a novel MB component...
  39. ncbi Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease
    Lynne J Hocking
    Department of Medicine and Therapeutics, University of Aberdeen, UK
    Hum Mol Genet 11:2735-9. 2002
    ..The gene encoding sequestosome 1 (SQSTM1/p62) maps to within the PDB3 critical region, and recent studies have identified a proline-leucine ..
  40. ncbi Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, 156 8585, Tokyo, Japan
    Neurosci Lett 342:41-4. 2003
    We examined the immunoreactivity of p62 in five cases of frontotemporal dementia (FTD) with ubiquitin-positive, tau-negative inclusions. Only one case had clinical features suggestive of motor neuron disease (MND)...
  41. ncbi Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone
    Barbara Ciani
    School of Chemistry, University Park, Nottingham NG7 2RD, United Kingdom
    J Biol Chem 278:37409-12. 2003
    The p62 protein (also known as SQSTM1) mediates diverse cellular functions including control of NFkappaB signaling and transcriptional activation...
  42. ncbi Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations
    James R Cavey
    School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
    J Bone Miner Res 20:619-24. 2005
    We have studied the effects of various PDB-causing mutations of SQSTM1 on the in vitro ubiquitin-binding properties of the p62 protein...
  43. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
    ..In this study, we report that polymerization of the polyubiquitin-binding protein p62/SQSTM1 yields protein bodies that either reside free in the cytosol and nucleus or occur within autophagosomes and ..
  44. ncbi Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue
    H Kitamura
    Department of Urology, Sapporo Medical University, Sapporo, Japan
    Histopathology 48:157-61. 2006
    ..The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue.
  45. ncbi Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone
    J R Cavey
    School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, United Kingdom
    Calcif Tissue Int 78:271-7. 2006
    Ubiquitin-associated (UBA) domain mutations of SQSTM1 are an important cause of Paget's disease of bone (PDB), which is a human skeletal disorder characterized by abnormal bone turnover...
  46. pmc The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation
    Pilar Martin
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Cantoblanco, Madrid, Spain
    EMBO J 25:3524-33. 2006
    ..We determine here the potential role of the signaling adapter p62 in T-cell polarization...
  47. pmc Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease
    Noriyoshi Kurihara
    VA Pittsburgh Healthcare System, Research and Development, Pittsburgh, Pennsylvania 15240, USA
    J Clin Invest 117:133-42. 2007
    ..Mutations in the p62 (sequestosome 1) gene occur in one-third of patients with familial Paget disease and in a minority of patients with sporadic ..
  48. ncbi Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone
    Jean Morissette
    Centre de recherche en endocrinologie moléculaire et oncologique, Centre de Recherche du Centre Hospitalier de l Universite Laval, Quebec, Quebec, Canada
    J Bone Miner Res 21:P38-44. 2006
    Mutations of the SQSTM1/p62 gene are commonly observed in PDB...
  49. pmc Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons
    Xiang Zhou
    Department of Cell Biology, Duke University Medical School, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 104:5842-7. 2007
    ..receptor complexes through promoting K63-polyubiquitination of Ulk1 and binding of Ulk1 to the scaffolding protein p62. These results and additional studies suggest that Ulk1/2 proteins regulate filopodia extension and neurite ..
  50. ncbi Autophagy-independent incorporation of GFP-LC3 into protein aggregates is dependent on its interaction with p62/SQSTM1
    Elena Shvets
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Autophagy 4:1054-6. 2008
    ..In addition, LC3 directly interacts with p62/SQSTM1 (hereafter named p62), a common constituent of protein aggregates...
  51. doi p62 protects SH-SY5Y neuroblastoma cells against H2O2-induced injury through the PDK1/Akt pathway
    Seong Ryong Heo
    Department of Biological Sciences, Hanseo University, Seosan, Chungnam 356 706, Republic of Korea
    Neurosci Lett 450:45-50. 2009
    The p62 protein has been identified as a major component of the protein aggregations associated with neurodegenerative disease. Oxidative insult has also been identified as a principal cause of neurodegenerative disease...
  52. doi Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget's disease of bone
    Dereen Najat
    School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
    J Bone Miner Res 24:632-42. 2009
    Mutations affecting the ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1/p62) are commonly found in Paget's disease of bone (PDB) and impair SQSTM1's ability to bind ubiquitin, resulting in dysregulated NF-kappaB signaling...
  53. pmc Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes
    Peter Kijun Kim
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:20567-74. 2008
    ..This targeting requires the ubiquitin-binding protein, p62, and is blocked by the Class III phosphatidylinositol 3-kinase (PI3K) inhibitor, 3-methyladenine (3-MA), or by ..
  54. ncbi p62 degradation by autophagy: another way for cancer cells to survive under hypoxia
    Panu M Jaakkola
    Turku Centre for Biotechnology, Turku University and Abo Akademi University, Tykistökatu 6B, Turku, Finland
    Autophagy 5:410-2. 2009
    ..Hypoxia activates mitophagy as well as macroautophagy that regulates carcinoma cell survival. p62/SQSTM1, a multifunctional protein that targets proteins to degradation by proteasomes and autophagy, is itself ..
  55. pmc The sequestosome 1/p62 attenuates cytokine gene expression in activated macrophages by inhibiting IFN regulatory factor 8 and TNF receptor-associated factor 6/NF-kappaB activity
    Ji Young Kim
    Laboratory of Molecular Growth Regulation, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 182:2131-40. 2009
    b>Sequestosome 1/p62 (p62) is a scaffold/adaptor protein with multiple functions implicated for neuronal and bone diseases. It carries a ubiquitin binding domain through which it mediates proteasome-dependent proteolysis...
  56. doi Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover
    Sarah Waters
    King s College London, Department of Medical and Molecular Genetics, London, UK
    FEBS Lett 583:1846-52. 2009
    ..Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3 and polyubiquitin-positive bodies...
  57. pmc PB1 domain interaction of p62/sequestosome 1 and MEKK3 regulates NF-kappaB activation
    Kazuhiro Nakamura
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 285:2077-89. 2010
    p62/Sequestosome 1 is a scaffold protein involved in the regulation of autophagy, trafficking of proteins to the proteasome, and activation of NF-kappaB...
  58. doi Epidemiological, clinical, and genetic characteristics of Paget's disease of bone in a rural area of Calabria, Southern Italy
    D Rendina
    Department of Clinical and Experimental Medicine, Federico II University Medical School, Via S Pansini, 5 80131 Naples, Italy
    J Endocrinol Invest 33:519-25. 2010
    ..The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania...
  59. pmc Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway
    Ian M Copple
    Medical Research Council Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, The University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, United Kingdom
    J Biol Chem 285:16782-8. 2010
    ..we have used immunopurification of Keap1 and mass spectrometry, in addition to immunoblotting, to identify sequestosome 1 (SQSTM1) as a cellular binding partner of Keap1...
  60. doi Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone
    Micaela Rios Visconti
    Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    J Bone Miner Res 25:2368-73. 2010
    ..Genetic factors play an important role in the pathogenesis of PDB, and the most important predisposing gene is SQSTM1, which is mutated in about 10% of patients...
  61. pmc p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects
    Bryan J Bartlett
    BioScience Center, San Diego State University, CA, USA
    Autophagy 7:572-83. 2011
    ..The p62/Ref(2)P family of proteins is involved in the autophagic clearance of cytoplasmic protein bodies or sequestosomes...
  62. pmc Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1
    Hye Mi Lee
    Department of Microbiology, Chungnam National University School of Medicine, Daejeon, Korea
    Immunol Cell Biol 90:601-10. 2012
    ..containing 3 (NLRP3) inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 (p62) in human macrophages...
  63. doi Paget's disease of bone: evidence for complex pathogenetic interactions
    Pui Yan Jenny Chung
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Semin Arthritis Rheum 41:619-41. 2012
    ..PDB etiology is not completely understood. In this review, current views on the etiology, clinical aspects, and PDB treatment are summarized and discussed...
  64. pmc p62 is a key regulator of nutrient sensing in the mTORC1 pathway
    Angeles Duran
    Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92307, USA
    Mol Cell 44:134-46. 2011
    The signaling adaptor p62 is a critical mediator of important cellular functions, owing to its ability to establish interactions with various signaling intermediaries. Here, we identify raptor as an interacting partner of p62...
  65. pmc p62 binding to protein kinase C ζ regulates tumor necrosis factor α-induced apoptotic pathway in endothelial cells
    Geun Young Kim
    Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Arterioscler Thromb Vasc Biol 32:2974-80. 2012
    Protein kinase C (PKC) ζ is a key pathological mediator of endothelial cell apoptosis. p62 is a scaffold protein that regulates several cell signaling pathways by binding to target proteins...
  66. pmc Bcl-2-dependent upregulation of autophagy by sequestosome 1/p62 in vitro
    Liang Zhou
    Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei 230027, China
    Acta Pharmacol Sin 34:651-6. 2013
    To investigate whether sequestosome 1/p62 (p62), a key cargo adaptor protein involved in both the ubiquitin-proteasome system and the autophagy-lysosome system, could directly regulate autophagy in vitro.
  67. doi Cleavage of sequestosome 1/p62 by an enteroviral protease results in disrupted selective autophagy and impaired NFKB signaling
    Junyan Shi
    James Hogg Research Center Providence Heart Lung Institute St Paul s Hospital and Department of Pathology and Laboratory Medicine University of British Columbia Vancouver, BC Canada
    Autophagy 9:1591-603. 2013
    The adaptor protein, sequestosome 1 (SQSTM1)/p62, plays an essential role in mediating selective autophagy. It serves as an autophagy receptor targeting ubiquitinated proteins to autophagosomes for degradation...
  68. doi Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy
    Yoshinobu Ichimura
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Mol Cell 51:618-31. 2013
    ..Here, we show that phosphorylation of the autophagy-adaptor protein p62 markedly increases p62's binding affinity for Keap1, an adaptor of the Cul3-ubiquitin E3 ligase complex ..
  69. pmc Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin
    Naonobu Fujita
    Department of Genetics, Graduate School of Medicine, 2 Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, 3 Department of Molecular Virology, Research Institute for Microbial Diseases, 4 Department of Host Defense, WPI Immunology Frontier Research Center, 5 Department of Host Defense, Research Institute for Microbial Disease, and 6 Core Instrumentation Facility, Research Institute for Microbial Disease, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Cell Biol 203:115-28. 2013
    ..Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3. ..
  70. pmc p62/sequestosome-1 up-regulation promotes ABT-263-induced caspase-8 aggregation/activation on the autophagosome
    Shengbing Huang
    From the Departments of Medicine and Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota 55905 and
    J Biol Chem 288:33654-66. 2013
    ..p62/sequestosome 1 is a multifunctional protein and a signaling hub that shuttles ubiquitinated proteins to the lysosome during ..
  71. pmc Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region
    I Park
    Division of Tumor Virology, Dana Farber Cancer Institute, Boston, MA, USA
    Proc Natl Acad Sci U S A 92:12338-42. 1995
    A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56lck has been identified...
  72. pmc Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain
    I Joung
    Division of Tumor Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:5991-5. 1996
    A novel human cDNA encoding a cytosolic 62-kDa protein (p62) that binds to the Src homology 2 (SH2) domain of p56lck in a phosphotyrosine-independent manner has been cloned...
  73. ncbi Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies
    E Kuusisto
    1Department of Neuroscience and Neurology, Section of Neuropathology, University of Kuopio, P O Box 1627, FIN 70211 Kuopio, Finland
    Neuroreport 12:2085-90. 2001
    We examined the immunoreactivity of ubiquitin-binding protein p62 and its association with ubiquitin (Ub), alpha-synuclein, and paired helical filament (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies...
  74. pmc Paget disease of bone: mapping of two loci at 5q35-qter and 5q31
    N Laurin
    Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, QC, Canada G1V 4G2
    Am J Hum Genet 69:528-43. 2001
    ..It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively.
  75. ncbi Mallory body--a disease-associated type of sequestosome
    Cornelia Stumptner
    Department of Pathology, School of Medicine, University of Graz, Graz, Austria
    Hepatology 35:1053-62. 2002
    Mallory bodies (MBs) consist of abnormal keratins, ubiquitin, heat shock proteins, and the protein p62. p62 is encoded by an immediate-early response gene that rapidly responds to a variety of extracellular signals involved in cell ..
  76. ncbi p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells
    H Garrett R Thompson
    Department of Biomedical Engineering, University of California, CA 92697 2715, USA
    Oncogene 22:2322-33. 2003
    b>p62 is a multifunctional cytoplasmic protein able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin-proteasome pathway...
  77. ncbi PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62
    Michael I Wilson
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Mol Cell 12:39-50. 2003
    ..members of the PB1 domain family, including the atypical protein kinase C zeta (PKC zeta) and its partners Par6 and p62 (ZIP, sequestosome)...
  78. ncbi Three novel mutations in SQSTM1 identified in familial Paget's disease of bone
    Teresa L Johnson-Pais
    Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Bone Miner Res 18:1748-53. 2003
    Mutations in Sequestosome 1 (SQSTM1) have been shown to segregate with familial Paget's disease of bone (PDB)...
  79. ncbi Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson's disease
    Kazuhiro Nakaso
    Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36 1, Nishimachi, Yonago, 683 8504, Japan
    Brain Res 1012:42-51. 2004
    ..Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy ..
  80. ncbi Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences
    Lynne J Hocking
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
    J Bone Miner Res 19:1122-7. 2004
    Three novel missense mutations of SQSTM1 were identified in familial PDB, all affecting the UBA domain...
  81. pmc Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation
    M Lamar Seibenhener
    Program in Cell and Molecular Biosciences, Department of Biological Sciences, Auburn University, AL 36849, USA
    Mol Cell Biol 24:8055-68. 2004
    Herein, we demonstrate that the ubiquitin-associated (UBA) domain of sequestosome 1/p62 displays a preference for binding K63-polyubiquitinated substrates...
  82. ncbi The kinase domain of titin controls muscle gene expression and protein turnover
    Stephan Lange
    Muscle Signalling and Development, Randall Division, King s College London, London SE1 1UL, UK
    Science 308:1599-603. 2005
    ..Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the ..
  83. ncbi Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity
    Zhiyou Wang
    Department of Biological Sciences, Hunter College of City University of New York, 695 Park Avenue, New York, NY 10021, USA
    Mol Cell Neurosci 29:222-31. 2005
    ..We report that prostaglandin J2 (PGJ2), an endogenous product of inflammation, up-regulates sequestosome 1/p62 in a time- and dose-dependent manner in human neuroblastoma SK-N-SH cells...
  84. ncbi Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation
    Jeganathan Ramesh Babu
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, AL 36849, USA
    J Neurochem 94:192-203. 2005
    ..Employing confocal and immunoelectron microscopy, we find that the ubiquitin-associating protein sequestosome1/p62, co-localizes to aggregates isolated from AD but not control brain, along with the E3 ubiquitin ligase, TRAF6...
  85. ncbi The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination
    Marie W Wooten
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Alabama 36849, USA
    J Biol Chem 280:35625-9. 2005
    b>Sequestosome 1/p62 is a scaffolding protein with several interaction modules that include a PB1 dimerization domain, a TRAF6 (tumor necrosis factor receptor-associated factor 6) binding site, and a ubiquitin-associating (UBA) domain...
  86. ncbi Genetics of Paget's disease of bone
    Laetitia Michou
    Clinical Genetics Unit, Hopital Lariboisiere, Paris, France
    Joint Bone Spine 73:243-8. 2006
    ..There is sound evidence incriminating Sequestosome 1 (SQSTM1) on the long arm of chromosome 5 (5q35-qter), of which nine mutations have been described in Paget's ..
  87. ncbi Immunoreactivities of p62, an ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis
    Yuji Mizuno
    Department of Neurology, Gunma University Graduate School of Medicine, 3 39 22 Showa machi, Maebashi, Gunma 371 8511, Japan
    J Neurol Sci 249:13-8. 2006
    An ubiquitin-binding protein, p62, is one of the components of the ubiquitin-containing inclusions in several human neurodegenerative diseases...
  88. ncbi Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American family
    G Beyens
    Department of Medical Genetics, University and University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
    Calcif Tissue Int 79:281-8. 2006
    ..Meanwhile, the PDB-causing gene from the PDB3 region on chromosome 5q35 has been identified as the SQSTM1 gene...
  89. ncbi Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Cell 131:1149-63. 2007
    ..We report that the ubiquitin- and LC3-binding protein "p62" regulates the formation of protein aggregates and is removed by autophagy...
  90. ncbi Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch
    Jed Long
    School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom
    J Biol Chem 283:5427-40. 2008
    The p62 protein functions as a scaffold in signaling pathways that lead to activation of NF-kappaB and is an important regulator of osteoclastogenesis...
  91. doi Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins
    Marie W Wooten
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 283:6783-9. 2008
    b>Sequestosome 1 (SQSTM1)/p62 is an interacting partner of the atypical protein kinase C zeta/iota and serves as a scaffold for cell signaling and ubiquitin binding, which is critical for several cell functions in vivo such as ..
  92. doi Specific regulation of cytokine-dependent p38 MAP kinase activation by p62/SQSTM1
    Kayoko Kawai
    Antibiotics Laboratory and Bioarchitect Research Group, DRI, RIKEN, 2 1 Hirosawa, Wako, Saitama, 351 0198, Japan
    J Biochem 143:765-72. 2008
    We have previously shown that p62/SQSTM1 binds to p38. In this study, we identified two association domains of p62 to p38 by conducting co-immunoprecipitation experiments...
  93. doi Founder effect in different European countries for the recurrent P392L SQSTM1 mutation in Paget's Disease of Bone
    Pui Yan Jenny Chung
    Department of Medical Genetics, University and University Hospital of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium
    Calcif Tissue Int 83:34-42. 2008
    ..Mutations in the sequestosome1 (SQSTM1) gene cause PDB in about one-third of familial PDB cases and in 2.4-9...
  94. ncbi NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets
    Vladimir Kirkin
    Institute of Biochemistry II, Goethe University, Frankfurt Main, Germany
    Autophagy 5:732-3. 2009
    ..p62/SQSTM1 was the first protein shown to bind both target-associated ubiquitin (Ub) and LC3 conjugated to the phagophore ..
  95. doi Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling
    Zhaoyu Jin
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 137:721-35. 2009
    ..The ubiquitin-binding protein p62/sequestosome-1 promoted aggregation of CUL3-modified caspase-8 within p62-dependent foci, leading to full ..
  96. pmc The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts
    Estelle Chamoux
    Division of Rheumatology, Faculty of Medicine, University of Sherbrooke, 3001, Sherbrooke, Quebec, Canada J1H 5N4
    Mol Endocrinol 23:1668-80. 2009
    Mutations of the gene encoding p62/SQSTM1 have been described in Paget's disease of bone (PDB), identifying p62 as an important player in osteoclast signaling...
  97. doi The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway
    Yiyu T Zheng
    Cell Biology Program, Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    J Immunol 183:5909-16. 2009
    ..Autophagy of ubiquitinated cargo requires p62 (also known as SQSTM1), an adaptor protein with multiple protein-protein interaction domains, including a ubiquitin-associated (UBA) ..
  98. doi Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling
    Jed Long
    Centre for Biomolecular Sciences, University Park, Nottingham NG7 2RD, UK
    J Mol Biol 396:178-94. 2010
    The ubiquitin (Ub)-binding p62 scaffold protein (encoded by the SQSTM1 gene) regulates a diverse range of signalling pathways leading to activation of the nuclear factor kappa B (NF-kappaB) family of transcription factors and is an ..
  99. pmc Nix is a selective autophagy receptor for mitochondrial clearance
    Ivana Novak
    Mediterranean Institute for Life Sciences, Mestrovicevo setaliste bb, HR 21000 Split, Croatia
    EMBO Rep 11:45-51. 2010
    ..Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation...
  100. pmc Nucleocytoplasmic shuttling of p62/SQSTM1 and its role in recruitment of nuclear polyubiquitinated proteins to promyelocytic leukemia bodies
    Serhiy Pankiv
    Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 285:5941-53. 2010
    p62, also known as sequestosome1 (SQSTM1), A170, or ZIP, is a multifunctional protein implicated in several signal transduction pathways...
  101. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
    ..In addition, the autophagic adaptor p62/SQSTM1 is recruited to mitochondrial clusters and is essential for the clearance of mitochondria...

Research Grants76

  1. Mechanisms of Ubiquitin Trafficking in Neurons
    Michael C Wooten; Fiscal Year: 2013
    ..b>Sequestosome 1/p62 is predominantly expressed in the hippocampus, the center of learning and memory, where it serves as a ..
  2. Role of p62 in Protein Aggregation and Neurodegeneration in ALS
    Haining Zhu; Fiscal Year: 2009
    ..P62/Sequestosome 1 (referred as p62 in this proposal) is a multifunctional protein involved in both of the two major protein ..
  3. Arunabh Bhattacharya; Fiscal Year: 2014
    ..autophagic pathway will be determined by measuring the expression of autophagic proteins (Atg-7, LC-3II/LC-3I, p62) and the autophagic flux through the pathway and activation of ubiquitin-proteasome pathway by measuring proteasome ..
  4. Junichi Sadoshima; Fiscal Year: 2014
    ..direct protein-protein interaction with Beclin1, thereby causing an accumulation of protein aggregates through p62, an ubiquitin interacting protein...
  5. Molecular mechanism underlying Frontotemporal Lobar Regeneration
    David Medina; Fiscal Year: 2013
    ..Additionally these changes correlate with a significant decrease of the ubiquitin binding protein p62, which serves as shuttling factor for select ubiquitinated proteins, such as TDP-43, towards autophagy ..
  6. Wei Xing Zong; Fiscal Year: 2016
    ..This caspase-8 activation is mediated by its association with a ubiquitin-binding protein SQSTM1/p62 and an autophagy-related protein microtubule-associated protein light chain 3 (LC3)...
  7. Autophagy and human islet amyloid polypeptide in animal models of type 2 diabetes
    Jacqueline Rivera; Fiscal Year: 2013
    ..e. LC3II, p62, and Atg7) and use of the gold standard in the field, electron microscopy...
  8. Meiosis, SUMOylation and the ZIP3 Protein: Parallel Studies in Mouse and Yeast.
    Neil Hunter; Fiscal Year: 2012
    ..To examine the role of mammalian ZIP3/RNF212, we have constructed a Zip3-/- knock-out mouse...
  9. Stephen B Howell; Fiscal Year: 2014
    ..ceruloplasmin by ATP7B, and dynactin that links vesicles to the motor protein dynein and microtubules and whose p62 subunit is known to interact with ATP7B in a Cu-dependent manner...
  10. Steven M Lipkin; Fiscal Year: 2015
    ..Intestinal goblet, Paneth cells and macrophages have increased ER stress. p62 and LC3-II, essential autophagy genes, accumulate with AGR2 knockdown...
  11. A Phase 0 Trial of Hydroxychloroquine in Patients with Stage III and IV Resectabl
    Janice Mehnert; Fiscal Year: 2010
    ..In addition, our group has discovered that autophagy deficient tumors under stress accumulate p62, a polyubiquitin binding protein that delivers aggregates to the lysosome for degradation, as well as several ..
  12. Michael S Kilberg; Fiscal Year: 2014
    ..Two of these isoforms, full- length ATF3 (ATF3-FL) and a form with a truncated leucine zipper, ATF3?Zip3, are induced in expression by low protein diet in vivo or by amino acid deprivation of cultured cells...
  13. The role of phosphorylation of Ulk1 by GSK-3b in myocardial autophagy and aging
    Peiyong Zhai; Fiscal Year: 2013
    ..Immunoblotting of aging marker will also be carried out. Immunoblotting of p62 and LC3, and measurements of red and yellow puncta in images taken from cardiac sections of mRFP-GFP-LC3 transgenic ..
  14. Cynthia A Lemere; Fiscal Year: 2014
    ..C3fl/fl mice from Aim 1 to ubiquitin-promoter driven Cre-Estrogen receptor 2 mice, treat the mice with tamoxifen at P60, and examine synapses, neurons and glia in hippocampus at 4 mo and 12 mo of age...
  15. Rhea M Sumpter; Fiscal Year: 2014
    ..We confirmed that one of these genes, the E3 ubiquitin (Ub) ligase and p62- interacting protein, Smurf1, is a novel virophagy factor for Sindbis virus (SIN) and herpes simplex virus (HSV)-1...
  16. Michael Karin; Fiscal Year: 2016
    ..changes in Ikk[unreadable]?pan mice are impaired autophagy, accumulation of the ubiquitin binding chaperone p62 and ER stress...
  17. Margaret Kielian; Fiscal Year: 2016
    ..Furin processing converts the alphavirus p62 companion protein to mature E2 and an E3 peptide...
  18. Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
    AMY JOY MACQUEEN; Fiscal Year: 2011
    ..b>Zip3, on the other hand, plays a role in preventing SC assembly on chromosomes...
  19. Selective Delivery of a novel bacterial adjuvant for multipurpose vaccination
    GREGOIRE STEPHANE LAUVAU; Fiscal Year: 2013
    ..Our current data also suggest that induction of these cells is likely to depend on one bacterial protein, the p60 autolysin, a virulence factor of the bacteria, which functions to digest peptidoglycan (PGN) cell walls...
  20. 5500 QTRAP
    John W Turk; Fiscal Year: 2010
    ..P41-RR00954) and also serves as a core MS laboratory for the WU Diabetes Research and Training Center (DRTC, P60-DK20579) and the WU Clinical Nutrition Research Unit (CNRU, P30-DK56341) that are supported by NIDDK...
  21. Loss-of-function mechanisms in Huntington's Disease
    Scott O Zeitlin; Fiscal Year: 2013
    ..First, ?Q-htt may mediate the enhanced recognition of mutant htt aggregates by p62/SQSTM1, a polyubiquitin binding protein that can target such aggregates for autophagic degradation...
  22. Nihal Ahmad; Fiscal Year: 2014
    ..studies have suggested that a diminished expression of Zn transporter proteins (ZIPs), especially ZIP1, ZIP2 and ZIP3 may be associated with this metabolic transformation...
  23. Autophagy, p62 and the Nrf2 Intersect to Protect Against Tau Toxicity
    Gail V W Johnson; Fiscal Year: 2013
    ..2. That the Nrf2 pathway plays a role in facilitating the degradation of pathological forms of tau. 3. That activation of the Nrf2 or autophagy pathway results in increased survival of cells that express pathological forms of tau. ..
  24. Center for Research on Improving the Treatment of Drug Abuse
    CHARLES P O'BRIEN; Fiscal Year: 2012
    This is a competing renewal application for a P60 Center that was formed in 1987 with the theme of, improving treatment of addiction...
  25. Laurel L Lenz; Fiscal Year: 2016
    ..Our prior studies with L. monocytogenes identified a bacterial protein, p60, whose expression and secretion from the bacterium is required for pathogenicity in the mouse model of systemic ..
  26. Active Subversion of Innate Immunity by Bacterial LysM Protein
    Laurel L Lenz; Fiscal Year: 2011
    ..Our prior studies with L. monocytogenes identified a bacterial protein, p60, whose expression and secretion from the bacterium is required for pathogenicity in the mouse model of systemic ..
  27. Jennifer C Fung; Fiscal Year: 2015
    ..To reduce the complexity of the problem, we propose to introduce a zip3 mutation that 1) limits the number of synapsing chromosomes to as low as one and 2) changes nucleation from ..
  28. Joanna C Bakowska; Fiscal Year: 2016
    ..droplets critical components that are important in membrane trafficking events along the autophagy pathway (namely p62 and a specific endosomal sorting complex required for transport-III protein [ESCRT-III])...
  29. Motivational Interviewing and Physical Activity Behavior Change in Arthritis
    Linda Ehrlich-Jones; Fiscal Year: 2012
    ..Finally, the NIAMS P60-funded Multidisciplinary Clinical Research Center in Rheumatology and the NCRR UL1-funded CTSA provide Northwestern ..
  30. Barbara J Mason; Fiscal Year: 2016
    ..For this renewal application, the TSRI-ARC will be a P60 consisting of 9 components plus an Educational Component...
  31. Repressing HIF-1: targets and mechanisms
    Nianli Sang; Fiscal Year: 2012
    ..events might modify the function and interactions of the heat shock protein machinery with HIF-1a and an acetylated p60 protein...
  32. Gene Expression in Rat Cochlea Following Loss of Hair Cells
    Erin Bailey; Fiscal Year: 2013
    ..corresponds to the onset of SGN death, a statistically significant amount of SGN degeneration has occurred by P32, P60 is midway through the period of degeneration, and at P90 few SGNs remain...
  33. Edward M Campbell; Fiscal Year: 2015
    ..In the second aim, we will define the role of the protein p62/sequestosome1 in regulating the degradation of TRIM5alpha...
  34. TWO TYPES OF MONOAMINE OXIDASE
    Jean Chen Shih; Fiscal Year: 2013
    ..5-HT levels will be determined by HPLC. Aggression and other related behaviors will be tested in adult mice (P60)...
  35. TAMARA J RICHARDS; Fiscal Year: 2016
    ..These animals are used in research supported by multiple R01s, U01s, the Portland Alcohol Research Center (PARC) P60 grant, and several VA Merit Review Grants...
  36. P62, Protein Aggregation and Fatty Liver Disease
    Martin Obin; Fiscal Year: 2005
    ..characteristic "inclusion bodies," which are enriched for aggregates of ubiquitinated, misfolded protein and p62/sequestosome-1, a ubiquitin chainbinding protein that traffics damaged polypeptides to the sequestosome (aggresome) ..
  37. Obesity-induced inflammation and insulin resistance by the p62/PKCzeta signaling
    Jorge Moscat; Fiscal Year: 2012
    ..This project will determine how a cell signaling complex assembled by p62/Sqstm1 and PKC6 regulates obesity-associated inflammation and insulin resistance in vivo, laying the groundwork for the ..
  38. Elizabeth P Henske; Fiscal Year: 2016
    ..In Aim 3, we will address the hypothesis that p62/sequestosome1-dependent signaling networks promote the growth and survival of TSC2-deficient cells...
  39. The p62/atypical PKC signaling complex in Th2 differentiation and asthma
    Jorge Moscat; Fiscal Year: 2012
    ..This proposal is based on our previous studies of atypical PKCs and p62 signaling pathways involved in Th2 differentiation...
  40. Harvard Older Americans Independence Center Grant
    Lewis Lipsitz; Fiscal Year: 2010
    ..our application to renew the Harvard Older Americans Independence Center (OAIC), which was previously funded by a P60 mechanism for 15 years...
  41. Role and mechanism of action of p62/Sqstm1 in Ras-induced tumorigenesis in lung
    Jorge Moscat; Fiscal Year: 2013
    ..The atypical PKCs (aPKCs) and their adapter p62 are implicated in the control of NF-[unreadable]B activation...
  42. TREATMENT OF ADDICTIONS-BIOLOGICAL CORRELATES
    Mary J Kreek; Fiscal Year: 2012
    ..Our NIH-NIDA P60 Treatment Research Center, "Treatment of Addictions: Biological Correlates," will continue to identify and study ..
  43. Translational Centerfor the Neurobehaviral Study of Alcohol
    Jeffrey L Weiner; Fiscal Year: 2012
    ..alcohol research at WFUHS to develop a translational alcohol research program that will successfully compete for a P60 center grant within the next five years...
  44. Gregory L Holmes; Fiscal Year: 2015
    ..of place cell firing (phase modulation, phase precession) will be studied in freely moving rats at P20 and P60 in a delayed spatial alternation task, and place cell properties will be compared between correct and incorrect ..
  45. Eric H Baehrecke; Fiscal Year: 2015
    ..to: (1) determine Atg6 mutant cellular defects, (2) investigate the genetic relationship between Atg6, Ref(2)P/p62, NF-kB and tissue overgrowth, and (3) characterize novel factors and pathways that are involved in Atg6-regulated ..
  46. Local Tobacco Policy and Youth Smoking
    Joel W Grube; Fiscal Year: 2012
    ..J. Paschall and J.W. Grube) that is part of a currently funded NIAAA Center Grant (P60 AA006282-26, Environmental Approaches to Prevention;P.I.: P. Gruenewald)...
  47. Cincinnati Multidisciplinary Clinical Research Center
    DANIEL JOE LOVELL; Fiscal Year: 2012
    ..application, from Cincinnati Children's Hospital Medical Center, is a competing continuation of our existing P60 Multidisciplinary Clinical Research Center grant and is complementary to our ongoing P30 Cincinnati Rheumatic ..
  48. James R McKay; Fiscal Year: 2014
    ..I am currently funded by a NIDA R01, a major project in a NIDA-funded P60, a NIAAA P01 Center, and a NIAAA R01. All of these projects are randomized clinical trials...
  49. Center on Antisocial Drug Dependence: The Genetics of HIV Risk Behaviors
    John K Hewitt; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): This revised proposal requests continued support for a Comprehensive P60 Center to extend our study of antisocial drug dependence to encompass its implications for HIV/AIDS...
  50. Victor M Hesselbrock; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): This P60 application from the University of Connecticut Alcohol Research Center (UCONN ARC) requests five years of continued funding for the Center's research programs on vulnerability to alcohol ..
  51. MARC: Risk Mechanisms in Alcoholism and Comorbidity
    Andrew C Heath; Fiscal Year: 2013
    This P60 application is the competing renewal application for the multi-site Multi-disciplinary Alcoholism Research Center (MARC)...
  52. James P Lash; Fiscal Year: 2016
    ..provided by the UIC Center for Clinical Translational Science (CCTS), the UIC School of Public Health, and the UIC P60 Center for Excellence in Health Disparities. This K24 award will provide Dr...
  53. GENETIC BASES FOR DISEASES OF THE RANK SIGNALING PATHWAY
    STEVEN R MUMM; Fiscal Year: 2013
    ..other candidate genes in the OPG/RANKL/RANK/NF-?B signaling pathway for disease-causing mutations, including SQSTM1, VCP, TRAF6, aPKC, NIK, and others...
  54. VICTORIA BEHAR MITRANI; Fiscal Year: 2016
    This application proposes to renew the P60 Center of Excellence for Health Disparities Research: El Centro, at the University of Miami School of Nursing and Health Studies. In the four years since funded...
  55. Karina L Walters; Fiscal Year: 2016
    ..This application, in response to RFA-MD-11-003 "NIMHD Comprehensive Centers of Excellence (P60)" is designed to develop IWRI as a National Comprehensive Center of Excellence (COE) devoted to AIAN health and ..
  56. Mona N Fouad; Fiscal Year: 2016
    This application by the University of Alabama at Birmingham (UAB) proposes to expand our current NIMHD funded P60 Center of Excellence - "Comprehensive Minority and Health Disparities Research Center (MHDRC)" to generate new knowledge on ..
  57. Peter M Monti; Fiscal Year: 2014
    ..along, though both Operario and White have submitted alcohol applications as part of the candidate's pending P60 Center Grant Proposal...
  58. BERNADETTE MARIE BODEN-ALBALA; Fiscal Year: 2015
    ..RR024156) and the Northern Manhattan Center of Excellence in Minority Health and Health Disparities (NOCEMHD;P60 MD000206)...
  59. The development of topographic maps and connectivity in M1 and S1 of rats
    ADELE MARY HANDLEY SEELKE; Fiscal Year: 2010
    ..will be investigated in developing Long-Evans rats as postnatal days (P) 5, 10, 15, 20, and during adulthood (>P60). Experiment 1 will investigate the development of somatotopic maps within S1...
  60. Lance O Bauer; Fiscal Year: 2016
    ..The range of experiences available to our trainees aligns closely with the range of NIAAA P60, U10, and R01 grant support awarded to our faculty. Over the past 10 yrs, our program has matured...
  61. COLUMBIA CENTER FOR HEALTH OF URBAN MINORITIES (CHUM)
    Jose A Luchsinger; Fiscal Year: 2012
    This application represents a continuation and further development of our existing NCMHD P60 Center of Excellence, the Columbia Center for the Health of Urban Minorities (CHUM)...
  62. Darrell J Gaskin; Fiscal Year: 2016
    This application is in response to RFA-MD-11-002, "NIMHD Comprehensive Centers of Excellence (P60)." The applicant organization is the Johns Hopkins University, Bloomberg School of Public Health...
  63. Program Project Grant-Pathobiology of Paget's Disease
    G Roodman; Fiscal Year: 2007
    ..2) develop an in vivo model of Paget's disease using targeted expression of the MVNP gene and the mutant p62 gene linked to familial Paget's disease to OCL in vivo...
  64. Function and Mechanisms of the N-End Rule Pathway
    Yong Tae Kwon; Fiscal Year: 2007
    ..and the degradation of various proteins (Sindbis virus RNA polymerase, HIV integrase, the Listeria monocytogenes p60, RGS4 and RGS16, and the encephalomyocarditis virus 3C protease)...
  65. Mode of Action of SQSTM1 Mutations in Paget's Disease Bone
    Marc Hansen; Fiscal Year: 2007
    ..Predisposition to familial Paget's Disease has been linked to a number of loci, including the Sequestosome 1 (SQSTM1) locus where germline mutations have been identified in 40% of the familial cases...
  66. GTP BINDING PROTEINS AND INSULIN RECEPTOR SINGNALING
    CHIN SUNG; Fiscal Year: 1999
    ..consists of: the IR; the p85 subunit of phosphatidylinositol-3-kinase; Ras GTPase activating protein (GAP); and p62 GAP-associated protein...
  67. EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT
    Daniel Howard; Fiscal Year: 2004
    ..of multimillion dollar grant awards from the NIH National Center for Minority Health and Health Disparities (P60 and R24 funding mechanisms) and the Agency for Healthcare Quality and Research (R24 funding mechanism) as well as ..
  68. Discovery of Novel TLR Ligands with Adjuvant Properties
    Thomas Powell; Fiscal Year: 2005
    ..g., LLO and p60 from Listeria monocytogenes) and purified by state of the art biochemical techniques...