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
Products:     SQSTM1

Top Publications

  1. Pankiv S, Clausen T, Lamark T, Brech A, Bruun J, Outzen H, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007;282:24131-45 pubmed
    ..The polyubiquitin-binding protein p62/SQSTM1 is degraded by autophagy...
  2. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213-23 pubmed publisher
    Impaired selective turnover of p62 by autophagy causes severe liver injury accompanied by the formation of p62-positive inclusions and upregulation of detoxifying enzymes...
  3. Gennari L, Gianfrancesco F, Di Stefano M, Rendina D, Merlotti D, Esposito T, et al. SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone. J Bone Miner Res. 2010;25:1375-84 pubmed publisher
    Even though SQSTM1 gene mutations have been identified in a consistent number of patients, the etiology of Paget's disease of bone (PDB) remains in part unknown...
  4. Zheng Y, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell J. The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol. 2009;183:5909-16 pubmed publisher
    ..Autophagy of ubiquitinated cargo requires p62 (also known as SQSTM1), an adaptor protein with multiple protein-protein interaction domains, including a ubiquitin-associated (UBA) ..
  5. Kawai K, Saito A, Sudo T, Osada H. Specific regulation of cytokine-dependent p38 MAP kinase activation by p62/SQSTM1. J Biochem. 2008;143:765-72 pubmed publisher
    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...
  6. Merchant A, Smielewska M, Patel N, Akunowicz J, Saria E, Delaney J, et al. Somatic mutations in SQSTM1 detected in affected tissues from patients with sporadic Paget's disease of bone. J Bone Miner Res. 2009;24:484-94 pubmed publisher
    ..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...
  7. Geisler S, Holmström K, Skujat D, Fiesel F, Rothfuss O, Kahle P, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119-31 pubmed publisher
    ..In addition, the autophagic adaptor p62/SQSTM1 is recruited to mitochondrial clusters and is essential for the clearance of mitochondria...
  8. Teyssou E, Takeda T, Lebon V, Boillee S, Doukoure B, Bataillon G, et al. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol. 2013;125:511-22 pubmed publisher
    Mutations in SQSTM1 encoding the sequestosome 1/p62 protein have recently been identified in familial and sporadic cases of amyotrophic lateral sclerosis (ALS)...
  9. Chamoux E, Couture J, Bisson M, Morissette J, Brown J, Roux S. The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts. Mol Endocrinol. 2009;23:1668-80 pubmed publisher
    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...

More Information

Publications127 found, 100 shown here

  1. Chung P, Van Hul W. Paget's disease of bone: evidence for complex pathogenetic interactions. Semin Arthritis Rheum. 2012;41:619-41 pubmed publisher
    ..The PubMed database was searched using the keywords PDB, sequestosome1 (SQSTM1), valosin-containing protein (VCP), receptor activator of nuclear factor-?B (RANK), osteoprotegerin (OPG), RANK ..
  2. Kim G, Nigro P, Fujiwara K, Abe J, Berk B. p62 binding to protein kinase C ? regulates tumor necrosis factor ?-induced apoptotic pathway in endothelial cells. Arterioscler Thromb Vasc Biol. 2012;32:2974-80 pubmed publisher
    Protein kinase C (PKC) ? 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...
  3. Tung Y, Hsu W, Lee H, Huang W, Liao Y. The evolutionarily conserved interaction between LC3 and p62 selectively mediates autophagy-dependent degradation of mutant huntingtin. Cell Mol Neurobiol. 2010;30:795-806 pubmed publisher
    Mammalian p62/sequestosome-1 protein binds to both LC3, the mammalian homologue of yeast Atg8, and polyubiquitinated cargo proteins destined to undergo autophagy-mediated degradation...
  4. Najat D, Garner T, Hagen T, Shaw B, Sheppard P, Falchetti A, et al. Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget's disease of bone. J Bone Miner Res. 2009;24:632-42 pubmed publisher
    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...
  5. Ichimura Y, Komatsu M. Selective degradation of p62 by autophagy. Semin Immunopathol. 2010;32:431-6 pubmed publisher
    ..b>p62, one of the selective substrates for autophagy, plays a key role in the formation of cytoplasmic proteinaceous ..
  6. Tanji K, Maruyama A, Odagiri S, Mori F, Itoh K, Kakita A, et al. Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases. J Neuropathol Exp Neurol. 2013;72:18-28 pubmed publisher
    ..One of the Nrf2 targets, p62, has been known to be incorporated into a wide spectrum of cytoplasmic inclusions in neurodegenerative diseases and ..
  7. Luciani A, Villella V, Esposito S, Brunetti Pierri N, Medina D, Settembre C, et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat Cell Biol. 2010;12:863-75 pubmed publisher
    ..of beclin 1, leading to sequestration of phosphatidylinositol-3-kinase (PI(3)K) complex III and accumulation of p62, which regulates aggresome formation...
  8. Ichimura Y, Waguri S, Sou Y, Kageyama S, Hasegawa J, Ishimura R, et al. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell. 2013;51:618-31 pubmed publisher
    ..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 ..
  9. Wooten M, Geetha T, Seibenhener M, Babu J, Diaz Meco M, Moscat J. The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J Biol Chem. 2005;280:35625-9 pubmed
    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...
  10. Cemma M, Kim P, Brumell J. The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway. Autophagy. 2011;7:341-5 pubmed
    Autophagy is an innate immune defense against bacterial invasion. Recent studies show that two adaptor proteins, p62 and NDP52, are required for autophagy of the bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium)...
  11. Gao C, Cao W, Bao L, Zuo W, Xie G, Cai T, et al. Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nat Cell Biol. 2010;12:781-90 pubmed publisher
    ..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; ..
  12. Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, et al. The kinase domain of titin controls muscle gene expression and protein turnover. Science. 2005;308:1599-603 pubmed
    ..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 ..
  13. Noda N, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, et al. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008;13:1211-8 pubmed publisher
    ..incorporation of specific cargo molecules into autophagosomes, in which Atg8 and LC3 interact with Atg19 and p62, receptor proteins for vacuolar enzymes and disease-related protein aggregates, respectively...
  14. Visconti M, Langston A, Alonso N, Goodman K, Selby P, Fraser W, et al. Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone. J Bone Miner Res. 2010;25:2368-73 pubmed publisher
    ..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...
  15. Zhou L, Wang H, Ren H, Chen D, Gao F, Hu Q, et al. Bcl-2-dependent upregulation of autophagy by sequestosome 1/p62 in vitro. Acta Pharmacol Sin. 2013;34:651-6 pubmed publisher
    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...
  16. Sanz L, Sanchez P, Lallena M, Diaz Meco M, Moscat J. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999;18:3044-53 pubmed
    ..Here we show that the previously described aPKC-binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo...
  17. Copple I, Lister A, Obeng A, Kitteringham N, Jenkins R, Layfield R, et al. Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. J Biol Chem. 2010;285:16782-8 pubmed publisher
    ..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...
  18. Shvets E, Fass E, Scherz Shouval R, Elazar Z. The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes. J Cell Sci. 2008;121:2685-95 pubmed publisher
    ..The N-terminal region was found to be important for interaction between LC3 and p62/SQSTM1 (hereafter termed p62)...
  19. Lee J, Nagano Y, Taylor J, Lim K, Yao T. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol. 2010;189:671-9 pubmed publisher
    ..catalyzing mitochondrial ubiquitination, which in turn recruits ubiquitin-binding autophagic components, HDAC6 and p62, leading to mitochondrial clearance...
  20. Watanabe Y, Tanaka M. p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate. J Cell Sci. 2011;124:2692-701 pubmed publisher
    ..Here, we found that p62/SQSTM1, a multifunctional adaptor protein, was involved in the selective autophagic clearance of a non-ubiquitylated ..
  21. Kirkin V, Lamark T, Johansen T, Dikic I. NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets. Autophagy. 2009;5:732-3 pubmed
    ..p62/SQSTM1 was the first protein shown to bind both target-associated ubiquitin (Ub) and LC3 conjugated to the phagophore ..
  22. Novak I, Kirkin V, McEwan D, Zhang J, Wild P, Rozenknop A, et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010;11:45-51 pubmed publisher
    ..Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation. ..
  23. Into T, Inomata M, Niida S, Murakami Y, Shibata K. Regulation of MyD88 aggregation and the MyD88-dependent signaling pathway by sequestosome 1 and histone deacetylase 6. J Biol Chem. 2010;285:35759-69 pubmed publisher
    ..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 ..
  24. Fujita N, Morita E, Itoh T, Tanaka A, Nakaoka M, Osada Y, et al. Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin. J Cell Biol. 2013;203:115-28 pubmed publisher
    ..Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3. ..
  25. Qiang L, Zhao B, Ming M, Wang N, He T, Hwang S, et al. Regulation of cell proliferation and migration by p62 through stabilization of Twist1. Proc Natl Acad Sci U S A. 2014;111:9241-6 pubmed publisher
    The selective autophagy substrate p62 serves as a molecular link between autophagy and cancer. Suppression of autophagy causes p62 accumulation and thereby contributes to tumorigenesis...
  26. Geetha T, Wooten M. Structure and functional properties of the ubiquitin binding protein p62. FEBS Lett. 2002;512:19-24 pubmed
    ..g. the rat atypical protein kinase C-interacting protein (ZIP), the murine A170/signal transduction and adapter protein, and the human p62, a protein that binds the Src homology 2 domain of p56(..
  27. Falchetti A, Di Stefano M, Marini F, Ortolani S, Ulivieri M, Bergui S, et al. Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone. Calcif Tissue Int. 2009;84:20-37 pubmed publisher
    Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene...
  28. Yu H, Su J, Xu Y, Kang J, Li H, Zhang L, et al. p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins. Eur J Cancer. 2011;47:1585-94 pubmed publisher
    ..Here, we show a critical role for the ubiquitin-binding protein p62/SQSTM1 in cisplatin resistance in human ovarian cancer cells (HOCCs)...
  29. Duran A, Amanchy R, Linares J, Joshi J, Abu Baker S, Porollo A, et al. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol Cell. 2011;44:134-46 pubmed publisher
    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...
  30. Hirano M, Nakamura Y, Saigoh K, Sakamoto H, Ueno S, Isono C, et al. Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. Neurology. 2013;80:458-63 pubmed publisher
    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 ..
  31. Kirkin V, Lamark T, Sou Y, Bjørkøy G, Nunn J, Bruun J, et al. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009;33:505-16 pubmed publisher
    ..Recent studies have indicated the existence of specific receptors, such as p62, which link ubiquitinated targets to autophagosomal degradation pathways...
  32. Garner T, Long J, Layfield R, Searle M. Impact of p62/SQSTM1 UBA domain mutations linked to Paget's disease of bone on ubiquitin recognition. Biochemistry. 2011;50:4665-74 pubmed publisher
    The scaffold protein p62/SQSTM1 acts as a hub in regulating a diverse range of signaling pathways which are dependent upon a functional ubiquitin-binding C-terminal UBA domain...
  33. Heo S, Han A, Kwon Y, Joung I. p62 protects SH-SY5Y neuroblastoma cells against H2O2-induced injury through the PDK1/Akt pathway. Neurosci Lett. 2009;450:45-50 pubmed publisher
    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...
  34. Filimonenko M, Isakson P, Finley K, Anderson M, Jeong H, Melia T, et al. The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010;38:265-79 pubmed publisher
    ..Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L, and LC3...
  35. Rubino E, Rainero I, Chiò A, Rogaeva E, Galimberti D, Fenoglio P, et al. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology. 2012;79:1556-62 pubmed publisher
    ..Recently, mutations in the sequestosome 1 (SQSTM1) gene, which encodes p62 protein, have been reported in patients with ALS...
  36. Inami Y, Waguri S, Sakamoto A, Kouno T, Nakada K, Hino O, et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J Cell Biol. 2011;193:275-84 pubmed publisher
    Suppression of autophagy is always accompanied by marked accumulation of p62, a selective autophagy substrate...
  37. Cavey J, Ralston S, Sheppard P, Ciani B, Gallagher T, Long J, et al. Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone. Calcif Tissue Int. 2006;78:271-7 pubmed
    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...
  38. Waters S, Marchbank K, Solomon E, Whitehouse C, Gautel M. Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover. FEBS Lett. 2009;583:1846-52 pubmed publisher
    ..Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3 and polyubiquitin-positive bodies...
  39. Wild P, Farhan H, McEwan D, Wagner S, Rogov V, Brady N, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011;333:228-33 pubmed publisher
    ..We propose that phosphorylation of autophagy receptors might be a general mechanism for regulation of cargo-selective autophagy. ..
  40. Matsumoto G, Wada K, Okuno M, Kurosawa M, Nukina N. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell. 2011;44:279-89 pubmed publisher
    ..p62/SQSTM1 is a key molecule managing autophagic clearance of polyubiquitinated proteins...
  41. Babu J, Geetha T, Wooten M. Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation. J Neurochem. 2005;94:192-203 pubmed
    ..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...
  42. Tanji K, Zhang H, Mori F, Kakita A, Takahashi H, Wakabayashi K. p62/sequestosome 1 binds to TDP-43 in brains with frontotemporal lobar degeneration with TDP-43 inclusions. J Neurosci Res. 2012;90:2034-42 pubmed publisher
    ..As with ubiquitin, anti-p62/SQSTM1 (referred to as p62) antibody clearly immunostains these inclusions...
  43. Zhou X, Babu J, da Silva S, Shu Q, Graef I, Oliver T, et al. Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons. Proc Natl Acad Sci U S A. 2007;104:5842-7 pubmed
    ..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 ..
  44. D Eletto M, Farrace M, Rossin F, Strappazzon F, Giacomo G, Cecconi F, et al. Type 2 transglutaminase is involved in the autophagy-dependent clearance of ubiquitinated proteins. Cell Death Differ. 2012;19:1228-38 pubmed publisher
    ..Furthermore, p62-dependent peroxisome degradation is also impaired in the absence of TG2...
  45. Albagha O, Visconti M, Alonso N, Wani S, Goodman K, Fraser W, et al. Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease. J Bone Miner Res. 2013;28:2338-46 pubmed publisher
    ..by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations...
  46. Park I, Chung J, Walsh C, Yun Y, Strominger J, Shin J. 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. Proc Natl Acad Sci U S A. 1995;92:12338-42 pubmed
    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...
  47. Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171:603-14 pubmed
    ..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 ..
  48. Hiruma Y, Honjo T, Jelinek D, Windle J, Shin J, Roodman G, et al. Increased signaling through p62 in the marrow microenvironment increases myeloma cell growth and osteoclast formation. Blood. 2009;113:4894-902 pubmed publisher
    ..Sequestosome-1 (p62), an adapter protein that has no intrinsic enzymatic activity, serves as a platform to facilitate formation of ..
  49. Huang S, Okamoto K, Yu C, Sinicrope F. p62/sequestosome-1 up-regulation promotes ABT-263-induced caspase-8 aggregation/activation on the autophagosome. J Biol Chem. 2013;288:33654-66 pubmed publisher
    ..p62/sequestosome 1 is a multifunctional protein and a signaling hub that shuttles ubiquitinated proteins to the lysosome during ..
  50. Beyens G, Wuyts W, Cleiren E, de Freitas F, Tiegs R, Van Hul W. 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. Calcif Tissue Int. 2006;79:281-8 pubmed
    ..Meanwhile, the PDB-causing gene from the PDB3 region on chromosome 5q35 has been identified as the SQSTM1 gene...
  51. Matthews B, Naot D, Bava U, Callon K, Pitto R, McCowan S, et al. Absence of somatic SQSTM1 mutations in Paget's disease of bone. J Clin Endocrinol Metab. 2009;94:691-4 pubmed publisher
    ..Mutations in the SQSTM1 gene are found in about one third of families with Paget's disease and 8% of sporadic cases...
  52. Kim P, Hailey D, Mullen R, Lippincott Schwartz J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci U S A. 2008;105:20567-74 pubmed publisher
    ..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 ..
  53. Jin Z, Li Y, Pitti R, Lawrence D, Pham V, Lill J, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 2009;137:721-35 pubmed publisher
    ..The ubiquitin-binding protein p62/sequestosome-1 promoted aggregation of CUL3-modified caspase-8 within p62-dependent foci, leading to full ..
  54. Lau A, Wang X, Zhao F, Villeneuve N, Wu T, Jiang T, et al. A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol. 2010;30:3275-85 pubmed publisher
    ..Deregulation of autophagy causes upregulation of p62 and the formation of p62-containing aggregates, which are associated with neurodegenerative diseases and cancer...
  55. Lee H, Shin D, Yuk J, Shi G, Choi D, Lee S, et al. Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1. J Immunol. 2011;186:1248-58 pubmed publisher
    The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be an autophagy receptor that acts as a link between the ubiquitination and autophagy machineries...
  56. Bae S, Sung S, Oh S, Lim J, Lee S, Park Y, et al. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab. 2013;17:73-84 pubmed publisher
    ..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 ..
  57. Zatloukal K, Stumptner C, Fuchsbichler A, Heid H, Schnoelzer M, Kenner L, et al. p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol. 2002;160:255-63 pubmed
    ..Using 2D gel electrophoresis and mass spectrometry, we identified p62 as a novel MB component...
  58. Thompson H, Harris J, Wold B, Lin F, Brody J. p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells. Oncogene. 2003;22:2322-33 pubmed
    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...
  59. Kitamura H, Torigoe T, Asanuma H, Hisasue S, Suzuki K, Tsukamoto T, et al. Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue. Histopathology. 2006;48:157-61 pubmed
    ..The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue...
  60. Jain A, Lamark T, Sjøttem E, Larsen K, Awuh J, Øvervatn A, et al. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem. 2010;285:22576-91 pubmed publisher
    The p62/SQSTM1 (sequestosome 1) protein, which acts as a cargo receptor for autophagic degradation of ubiquitinated targets, is up-regulated by various stressors...
  61. Michou L, Morissette J, Gagnon E, Marquis A, DellaBadia M, Brown J, et al. Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population. Bone. 2011;48:456-60 pubmed publisher
    More than 20 mutations of the Sequestosome 1 (SQSTM1) gene have been reported in patients of European descent affected by Paget's disease of bone (PDB)...
  62. Itakura E, Mizushima N. p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding. J Cell Biol. 2011;192:17-27 pubmed publisher
    ..It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3...
  63. Cundy T, Naot D, Bava U, Musson D, Tong P, Bolland M. Familial Paget disease and SQSTM1 mutations in New Zealand. Calcif Tissue Int. 2011;89:258-64 pubmed publisher
    Genetic factors play an important role in the pathogenesis of Paget disease of bone (PDB). SQSTM1 is the most important disease-associated gene identified to date...
  64. Shi C, Shenderov K, Huang N, Kabat J, Abu Asab M, Fitzgerald K, et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol. 2012;13:255-63 pubmed publisher
    ..Assembled inflammasomes underwent ubiquitination and recruited the autophagic adaptor p62, which assisted their delivery to autophagosomes...
  65. Komatsu M, Kageyama S, Ichimura Y. p62/SQSTM1/A170: physiology and pathology. Pharmacol Res. 2012;66:457-62 pubmed publisher
    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...
  66. Wright T, Rea S, Goode A, Bennett A, Ratajczak T, Long J, et al. The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget's disease of bone. Bone. 2013;52:699-706 pubmed publisher
    Mutations affecting the Sequestosome 1 (SQSTM1) gene commonly occur in patients with the skeletal disorder Paget's disease of bone (PDB), a condition characterised by defective osteoclast differentiation and function...
  67. Nihira K, Miki Y, Ono K, Suzuki T, Sasano H. An inhibition of p62/SQSTM1 caused autophagic cell death of several human carcinoma cells. Cancer Sci. 2014;105:568-75 pubmed publisher
    p62/SQSTM1 (p62) is a multifunctional protein implicated in several signal transduction pathways and selectively degraded by autophagy, a process for lysosomal degradation of both protein and organelle...
  68. Donaldson K, Li W, Ching K, Batalov S, Tsai C, Joazeiro C. Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci U S A. 2003;100:8892-7 pubmed
    ..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 ..
  69. Seibenhener M, Babu J, Geetha T, Wong H, Krishna N, Wooten M. Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol. 2004;24:8055-68 pubmed
    Herein, we demonstrate that the ubiquitin-associated (UBA) domain of sequestosome 1/p62 displays a preference for binding K63-polyubiquitinated substrates...
  70. Long J, Gallagher T, Cavey J, Sheppard P, Ralston S, Layfield R, et al. Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch. J Biol Chem. 2008;283:5427-40 pubmed
    The p62 protein functions as a scaffold in signaling pathways that lead to activation of NF-kappaB and is an important regulator of osteoclastogenesis...
  71. Shvets E, Elazar Z. Autophagy-independent incorporation of GFP-LC3 into protein aggregates is dependent on its interaction with p62/SQSTM1. Autophagy. 2008;4:1054-6 pubmed
    ..In addition, LC3 directly interacts with p62/SQSTM1 (hereafter named p62), a common constituent of protein aggregates...
  72. Rea S, Walsh J, Ward L, Magno A, Ward B, Shaw B, et al. 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. J Bone Miner Res. 2009;24:1216-23 pubmed publisher
    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...
  73. Fan W, Tang Z, Chen D, Moughon D, Ding X, Chen S, et al. Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy. Autophagy. 2010;6:614-21 pubmed publisher
    ..plays a critical role in the clearance of ubiquitin aggregates, a process that is mediated by the ubiquitin binding protein p62. In addition to binding ubiquitin, p62 also interacts with LC3 and transports ubiquitin conjugates to ..
  74. Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou Y, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells. 2010;15:887-900 pubmed publisher
    ..In addition, p62/SQSTM1 (hereafter referred to as p62) was recruited to depolarized mitochondria after Parkin-directed ubiquitylation...
  75. Pan J, Ullman E, Dou Z, Zong W. Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes. Mol Cell Biol. 2011;31:3158-70 pubmed publisher
    ..caspase-8 oligomerization and activation are promoted through its interaction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light chain 3 (LC3), which are enriched at intracellular membranes in ..
  76. Shi J, Wong J, Piesik P, Fung G, Zhang J, Jagdeo J, et al. Cleavage of sequestosome 1/p62 by an enteroviral protease results in disrupted selective autophagy and impaired NFKB signaling. Autophagy. 2013;9:1591-603 pubmed publisher
    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...
  77. Kim J, Ozato K. 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. J Immunol. 2009;182:2131-40 pubmed publisher
    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...
  78. Lamark T, Perander M, Outzen H, Kristiansen K, Øvervatn A, Michaelsen E, et al. Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. J Biol Chem. 2003;278:34568-81 pubmed
    ..Among the last group, p62 and Par6 (partitioning-defective 6) are involved in coupling the aPKCs to signaling pathways involved in cell ..
  79. Nakaso K, Yoshimoto Y, Nakano T, Takeshima T, Fukuhara Y, Yasui K, et al. 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. Brain Res. 2004;1012:42-51 pubmed
    ..Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy ..
  80. Ding W, Ni H, Li M, Liao Y, Chen X, Stolz D, et al. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem. 2010;285:27879-90 pubmed publisher
    ..cyanide m-chlorophenylhydrazone (CCCP) that Parkin translocation resulted in mitochondrial ubiquitination and p62 recruitment to the mitochondria...
  81. Fusco C, Micale L, Egorov M, Monti M, D Addetta E, Augello B, et al. The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome. PLoS ONE. 2012;7:e40440 pubmed publisher
    ..Finally we demonstrate that TRIM50 colocalizes, interacts with and increases the level of p62, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of ..
  82. Sanz L, Diaz Meco M, Nakano H, Moscat J. The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway. EMBO J. 2000;19:1576-86 pubmed
    The atypical protein kinase C (aPKC)-interacting protein, p62, has previously been shown to interact with RIP, linking these kinases to NF-kappaB activation by tumor necrosis factor alpha (TNFalpha)...
  83. Kuusisto E, Salminen A, Alafuzoff I. Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. Neuroreport. 2001;12:2085-90 pubmed
    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...
  84. Arai T, Nonaka T, Hasegawa M, Akiyama H, Yoshida M, Hashizume Y, et al. Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62. Neurosci Lett. 2003;342:41-4 pubmed
    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)...
  85. Johnson Pais T, Wisdom J, Weldon K, Cody J, Hansen M, Singer F, et al. Three novel mutations in SQSTM1 identified in familial Paget's disease of bone. J Bone Miner Res. 2003;18:1748-53 pubmed
    Mutations in Sequestosome 1 (SQSTM1) have been shown to segregate with familial Paget's disease of bone (PDB)...
  86. Eekhoff E, Karperien M, Houtsma D, Zwinderman A, Dragoiescu C, Kneppers A, et al. Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations. Arthritis Rheum. 2004;50:1650-4 pubmed
    ..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...