Genomes and Genes
ubiquitin protein ligases
Summary: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
Publications428 found, 100 shown here
- Mutations in the parkin gene cause autosomal recessive juvenile parkinsonismT Kitada
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
Nature 392:605-8. 1998..Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'...
- Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligaseH Shimura
Department of Neurology, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
Nat Genet 25:302-5. 2000....
- Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complexNing Zheng
Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York 10021, USA
Nature 416:703-9. 2002..The structure suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold...
- The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53M Scheffner
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892
Cell 75:495-505. 1993..The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6...
- Function and regulation of cullin-RING ubiquitin ligasesMatthew D Petroski
Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Nat Rev Mol Cell Biol 6:9-20. 2005..In this review, we focus on the composition, regulation and function of cullin-RING ligases, and describe how these enzymes can be characterized by a set of general principles...
- Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutantsJessica C Greene
Department of Genome Sciences, University of Washington, P O Box 357730, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 100:4078-83. 2003....
- Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosisQing Zhong
Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
Cell 121:1085-95. 2005..Thus, Mule is a unique BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA damage-induced apoptosis...
- Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chainL Deng
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
Cell 103:351-61. 2000..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains...
- Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7Masayoshi Yada
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi ku, Fukuoka, Fukuoka, Japan
EMBO J 23:2116-25. 2004..Accumulation of c-Myc was also apparent in mouse Fbw7-/- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively...
- Themes and variations on ubiquitylationA M Weissman
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 1152, USA
Nat Rev Mol Cell Biol 2:169-78. 2001..A few years ago, we could only have dreamt of the complex arsenal of enzymes dedicated to ubiquitylation. Why has nature come up with so many ways of doing what seems to be such a simple job?..
- Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligasesN Zheng
Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Cell 102:533-9. 2000....
- The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradationMarkus Welcker
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Proc Natl Acad Sci U S A 101:9085-90. 2004..Because Fbw7 mediates the degradation of cyclin E, Notch, and c-Jun, as well as c-Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation during tumorigenesis...
- Association between early-onset Parkinson's disease and mutations in the parkin geneC B Lücking
INSERM Unité 289, Hopital de la Salpetriere, Paris
N Engl J Med 342:1560-7. 2000..Mutations in the parkin gene have recently been identified in patients with early-onset Parkinson's disease, but the frequency of the mutations and the associated phenotype have not been assessed in a large series of patients...
- Physiological functions of the HECT family of ubiquitin ligasesDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children, Ontario, Canada
Nat Rev Mol Cell Biol 10:398-409. 2009..The physiological functions of the yeast HECT E3 ligase Rsp5 are the best known, but the functions of HECT E3 enyzmes in metazoans are now becoming clearer from in vivo studies...
- UBE3A/E6-AP mutations cause Angelman syndromeT Kishino
Genetics Division, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Genet 15:70-3. 1997..Our results demonstrate that UBE3A mutations are one cause of AS and indicate a possible abnormality in ubiquitin-mediated protein degradation during brain development in this disease...
- Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkinNicole Exner
Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
J Neurosci 27:12413-8. 2007..Our results may therefore suggest that PINK1 deficiency in humans results in mitochondrial abnormalities associated with cellular stress, a pathological phenotype, which can be ameliorated by enhanced expression of parkin...
- Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascadeL Huang
Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Science 286:1321-6. 1999..The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3...
- The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradationG C Meacham
Department of Cell Biology and Cystic Fibrosis Center, University of Alabama Medical Center, 1918 University Boulevard, Birmingham, Alabama 35294 0005, USA
Nat Cell Biol 3:100-5. 2001..CHIP is a co-chaperone that converts Hsc70 from a protein-folding machine into a degradation factor that functions in endoplasmic-reticulum quality control...
- OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERADJohn C Christianson
Department of Biological Sciences and Bio X Program, Stanford University, Lorry Lokey Bldg, 337 Campus Drive, Stanford, CA 94305, USA
Nat Cell Biol 10:272-82. 2008..These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells...
- Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1G Levkowitz
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
Mol Cell 4:1029-40. 1999..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways...
- The E3 ubiquitin ligase Itch controls the protein stability of p63Mario Rossi
Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, United Kingdom
Proc Natl Acad Sci U S A 103:12753-8. 2006..These data suggest that Itch has a fundamental role in the mechanism that controls endogenous p63 protein levels and therefore contributes to regulation of p63 in physiological conditions...
- Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by DeltaMotoyuki Itoh
Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA
Dev Cell 4:67-82. 2003..This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells...
- Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligaseD M Koepp
Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA
Science 294:173-7. 2001..Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation...
- Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1Y Zhang
Departments of Neurology, Neuroscience, and Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287 0005, USA
Proc Natl Acad Sci U S A 97:13354-9. 2000..The loss of Parkin's ubiquitin-protein ligase function in familial-linked mutations suggests that this may be the cause of familial autosomal recessive Parkinson's disease...
- Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradationP Kavsak
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada
Mol Cell 6:1365-75. 2000..These studies thus define Smad7 as an adaptor in an E3 ubiquitin-ligase complex that targets the TGF beta receptor for degradation...
- The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemiaBenjamin J Thompson
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
J Exp Med 204:1825-35. 2007..Our data suggest that FBW7 is a novel tumor suppressor in T cell leukemia, and implicate the loss of FBW7 function as a potential mechanism of drug resistance in T-ALL...
- Mitochondrial dysfunction and oxidative damage in parkin-deficient miceJames J Palacino
Center for Neurologic Diseases, Brigham and Women s Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 279:18614-22. 2004....
- The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscleBrian A Clarke
Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139, USA
Cell Metab 6:376-85. 2007..These data identify the mechanism by which MYH is depleted under atrophy conditions and demonstrate that inhibition of a single E3 ligase, MuRF1, is sufficient to maintain this important sarcomeric protein...
- The ubiquitin ligase COP1 is a critical negative regulator of p53David Dornan
Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
Nature 429:86-92. 2004..Overall, these results indicate that COP1 is a critical negative regulator of p53 and represents a new pathway for maintaining p53 at low levels in unstressed cells...
- Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signalingWei Li
Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA
PLoS ONE 3:e1487. 2008..These findings suggest the existence of a new, Ub-mediated mechanism responsible for integration of mitochondria into the cellular environment...
- Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's diseaseH Shimura
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
Science 293:263-9. 2001..These findings demonstrate a critical biochemical reaction between the two PD-linked gene products and suggest that this reaction underlies the accumulation of ubiquitinated alpha-synuclein in conventional PD...
- The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysisP H Maxwell
Wellcome Trust Centre for Human Genetics, Oxford, UK
Nature 399:271-5. 1999..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
- Mechanisms underlying ubiquitinationC M Pickart
School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
Annu Rev Biochem 70:503-33. 2001..The new findings shed light on many aspects of E3 structure, function, and mechanism, but also emphasize that key features of E3 catalysis remain to be elucidated...
- Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53S Fang
Laboratory of Immune Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892 1152, USA
J Biol Chem 275:8945-51. 2000..However, this RING was ineffective in ubiquitination and proteasomal targeting of p53, suggesting that there may be specificity at the level of the RING in the recognition of heterologous substrates...
- Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligasesBing Hao
Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Mol Cell 26:131-43. 2007....
- FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitorsJennifer O'Neil
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
J Exp Med 204:1813-24. 2007....
- Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1Jarrod W Heck
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 107:1106-11. 2010..The broad conservation of Ubr ligases and the relevant chaperones indicates that these mechanisms will be important in understanding both basic and biomedical aspects of cellular proteostasis...
- Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnoverChristy J Fryer
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
Mol Cell 16:509-20. 2004..These findings suggest a role for MAM and CycC:CDK8 in the turnover of the Notch enhancer complex at target genes...
- The nucleoporin RanBP2 has SUMO1 E3 ligase activityAndrea Pichler
Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
Cell 108:109-20. 2002..Our findings place SUMOylation at the cytoplasmic filaments of the NPC and suggest that, at least for some substrates, modification and nuclear import are linked events...
- CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activityYuzuru Imai
Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351 0198, Japan
Mol Cell 10:55-67. 2002..Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity...
- Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesisH Zou
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
Science 285:418-22. 1999..The oncogenic nature of increased expression of vSecurin may result from chromosome gain or loss, produced by errors in chromatid separation...
- Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separinS B Buonomo
Research Institute of Molecular Pathology, University of Vienna, Austria
Cell 103:387-98. 2000..We show here that cleavage of Rec8 by separin at one of two different sites is necessary for the resolution of chiasmata and the disjunction of homologous chromosomes during meiosis...
- SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-boxC Bai
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
Cell 86:263-74. 1996..Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle...
- Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's diseaseSteven A Beasley
Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5C1
Proc Natl Acad Sci U S A 104:3095-100. 2007....
- Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductaseBao Liang Song
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Mol Cell 19:829-40. 2005..The current results identify gp78 as the E3 that initiates sterol-accelerated degradation of reductase, and Insig-1 as a bridge between gp78/VCP and the reductase substrate...
- FBXW7/hCDC4 is a general tumor suppressor in human cancerShahab Akhoondi
Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
Cancer Res 67:9006-12. 2007..Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer...
- The polycomb protein Pc2 is a SUMO E3Michael H Kagey
Department of Biochemistry and Molecular Genetics, Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA
Cell 113:127-37. 2003..These results demonstrate that Pc2 is a SUMO E3, and suggest that PcG bodies may be sumoylation centers...
- PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0Roger D Everett
MRC Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom
J Virol 80:7995-8005. 2006..We conclude that PML contributes to a cellular antiviral repression mechanism that is countered by the activity of ICP0...
- A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1Jianping Jin
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 23:709-21. 2006..These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication...
- Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complexB A Schulman
Cellular Biochemistry and Biophysics Program, Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Nature 408:381-6. 2000....
- Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligaseS Nakagawa
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855, USA
Mol Cell Biol 20:8244-53. 2000....
- Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complexMinghao Zhang
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
Mol Cell 20:525-38. 2005....
- An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeastR Ciosk
Research Institute of Molecular Pathology, Vienna, Austria
Cell 93:1067-76. 1998..We propose that the APC promotes sister separation not by destroying cohesins but instead by liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p...
- Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradationMarkus Welcker
Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Mol Cell 12:381-92. 2003..Thus, cyclin E turnover is controlled by multiple biological inputs and cannot be understood in terms of autophosphorylation alone...
- How proteolysis drives the cell cycleR W King
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
Science 274:1652-9. 1996..Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics...
- Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508Daisuke Morito
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
Mol Biol Cell 19:1328-36. 2008..Our data demonstrates that gp78 cooperates with RMA1 with E4-like activity in the ERAD of CFTRDeltaF508...
- Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencingRu Cao
Howard Hughes Medical Institute, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
Mol Cell 20:845-54. 2005..Our results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing...
- Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2Christian C Witt
Institute of Anesthesiology and Intensive Care, Universitatsklinikum Mannheim, Mannheim, Germany
EMBO J 27:350-60. 2008..Thus, combined inhibition of MuRF1/MuRF2 could provide a potent strategy to stimulate striated muscles anabolically and to protect muscles from sarcopenia during ageing...
- CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70Shu Bing Qian
Carolina Cardiovascular Biology Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Nature 440:551-5. 2006....
- Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivoMonte S Willis
Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599 7126, USA
Circ Res 100:456-9. 2007..These studies describe for the first time distinct and nonoverlapping functional characteristics of MuRF1 and MuRF2 in response to cardiac stress in vivo...
- TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activityMichaela U Gack
Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, 1 Pine Hill Drive, Southborough, Massachusetts 01772, USA
Nature 446:916-920. 2007..Thus, we demonstrate that TRIM25 E3 ubiquitin ligase induces the Lys 63-linked ubiquitination of RIG-I, which is crucial for the cytosolic RIG-I signalling pathway to elicit host antiviral innate immunity...
- A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formationH Zhu
Department of Biochemistry and Cell Biology and Institute for Cell and Developmental Biology, State University of New York, Stony Brook 11794 5215, USA
Nature 400:687-93. 1999..Smurf1 also enhances cellular responsiveness to the Smad2 (activin/TGF-beta) pathway. Thus, targeted ubiquitination of SMADs may serve to control both embryonic development and a wide variety of cellular responses to TGF-beta signals...
- A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell sizeMarkus Welcker
Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Curr Biol 14:1852-7. 2004..We suggest that interactions between c-Myc and Fbw7gamma within the nucleolus regulate c-Myc's growth-promoting function and that c-Myc activation is likely to be an important oncogenic consequence of Fbw7 loss in cancers...
- Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neuronsLeonard Petrucelli
Neurogenetics Laboratory, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
Neuron 36:1007-19. 2002..Therefore, parkin and alpha-synuclein are linked by common effects on a pathway associated with selective cell death in catecholaminergic neurons...
- E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkagesDevin E Christensen
Department of Biochemistry, University of Washington, Box 357350, Seattle, Washington 98195 7350, USA
Nat Struct Mol Biol 14:941-8. 2007..Thus, BRCA1 has the ability to direct the synthesis of specific polyubiquitin chain linkages, depending on the E2 bound to its RING...
- The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnoverLufen Chang
Division of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute at City of Hope, City of Hope National Medical Center, 1500 E Duarte Road, KCRB 3009, Duarte, CA 91010, USA
Cell 124:601-13. 2006..Thus, JNK antagonizes NF-kappaB during TNFalpha signaling by promoting the proteasomal elimination of c-FLIP(L)...
- FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiationMarkus Welcker
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA
Nat Rev Cancer 8:83-93. 2008..This Review focuses on structural and functional aspects of FBW7 and its role in the development of cancer...
- Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradationT Ebisawa
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, and Research for the Future Program, the Japan Society for the Promotion of Science, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
J Biol Chem 276:12477-80. 2001..These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor...
- Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycleKasia Hrecka
Cold Spring Harbor Laboratory, Bungtown Road, Cold Spring Harbor, NY 11724, USA
Proc Natl Acad Sci U S A 104:11778-83. 2007....
- The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activityRonen Ben-Saadon
Cancer and Vascular Biology Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Bat Galim, Haifa 31096, Israel
Mol Cell 24:701-11. 2006..The modification is required for Ring1B ability to monoubiquitinate H2A in vitro, unraveling an as yet undescribed mechanism for ligase activation via noncanonical self-ubiquitination...
- CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregationLeonard Petrucelli
Mayo Clinic, Jacksonville, FL 32224, USA
Hum Mol Genet 13:703-14. 2004..Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target...
- Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell deathHan Seok Ko
Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 25:7968-78. 2005..Moreover, these results have important implications for understanding the molecular mechanisms of neurodegeneration in PD...
- VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligasesTakumi Kamura
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Genes Dev 18:3055-65. 2004..These data suggest that the functions of the Cul2-Rbx1 and Cul5-Rbx2 modules are distinct...
- A regulatory link between ER-associated protein degradation and the unfolded-protein responseR Friedlander
Max Delbruck Centrum fur Molekulare Medizin, Berlin, Germany
Nat Cell Biol 2:379-84. 2000..However, when stress is applied, the UPR is required to increase ERAD activity. We thus demonstrate, for the first time, a regulatory loop between ERAD and the UPR, which is essential for normal growth of yeast cells...
- Mitochondrial function and morphology are impaired in parkin-mutant fibroblastsHeather Mortiboys
Academic Neurology Unit, Medical School, University of Sheffield, Sheffield, United Kingdom
Ann Neurol 64:555-65. 2008..The aim of our study was to determine mitochondrial function and morphology in parkin-mutant patients. We also investigated whether pharmacological rescue of impaired mitochondrial function may be possible in parkin-mutant human tissue...
- F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complexD Skowyra
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
Cell 91:209-19. 1997..SCF complexes couple protein kinase signaling pathways to the control of protein abundance...
- Biomedicine. Parkinson's--divergent causes, convergent mechanismsJ Timothy Greenamyre
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
Science 304:1120-2. 2004
- Ubiquitin-dependent proteolytic control of SUMO conjugatesKristina Uzunova
Institute for Genetics, University of Cologne, Zulpicher Strasse 47, Cologne, Germany
J Biol Chem 282:34167-75. 2007..Simultaneous inhibition of both mechanisms leads to severe phenotypic defects...
- Herpes simplex virus type 1 immediate-early protein ICP0 and is isolated RING finger domain act as ubiquitin E3 ligases in vitroChris Boutell
Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom
J Virol 76:841-50. 2002..We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome...
- A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligaseJ M Huibregtse
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 92:2563-7. 1995....
- Herpes simplex virus ICP0 promotes both histone removal and acetylation on viral DNA during lytic infectionAnna R Cliffe
Harvard Medical School, Department of Microbiology and Molecular Genetics, 200 Longwood Avenue, Boston, MA 02115, USA
J Virol 82:12030-8. 2008..This study provides evidence that ICP0 directly alters the chromatin structure of the HSV-1 genome during lytic infection, and this system will serve as a useful model for the reduction of histone load in higher eukaryotes...
- Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacityCornelia Hampe
Neurologie et Thérapeutique Expérimentale, INSERM U679 Université Pierre and Marie Curie, Paris, France
Hum Mol Genet 15:2059-75. 2006..The discovery of monoubiquitylated Parkin species in cells hints at a novel post-translational modification potentially involved in the regulation of Parkin function...
- Inactivation of hCDC4 can cause chromosomal instabilityHarith Rajagopalan
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Nature 428:77-81. 2004..Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion...
- Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkinSathya R Sriram
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hum Mol Genet 14:2571-86. 2005....
- Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulatorJ Michael Younger
Department of Cell and Developmental Biology, UNC Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
Cell 126:571-82. 2006..Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508...
- The F-box subunit of the SCF E3 complex is encoded by a diverse superfamily of genes in ArabidopsisJennifer M Gagne
Cellular and Molecular Biology Program and the Department of Horticulture, 1575 Linden Drive, University of Wisconsin, Madison, WI 53706, USA
Proc Natl Acad Sci U S A 99:11519-24. 2002..Collectively, the data shows that Arabidopsis has exploited the SCF complex and the ubiquitin/26S proteasome pathway as a major route for cellular regulation and that a diverse array of SCF targets is likely present in plants...
- The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3AM Runte
Institut fur Humangenetik, Universitatsklinikum Essen, 45122 Essen, Germany
Hum Mol Genet 10:2687-700. 2001..As we have not obtained any evidence for other genes in this region, which, from the mouse data appears to be critical for the neonatal Prader-Willi syndrome phenotype, a lack of these snoRNAs may be causally involved in this disease...
- The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferationSovana Adhikary
Institute for Molecular Biology and Tumor Research, University of Marburg, Emil Mannkopff Str 2, 35033 Marburg, Germany
Cell 123:409-21. 2005..Our results suggest that site-specific ubiquitination regulates the switch between an activating and a repressive state of the Myc protein, and they suggest a strategy to interfere with Myc function in vivo...
- The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptorXiaoyun Wen
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
J Biol Chem 282:27046-57. 2007..Vpr, thus, functions like the HIV1 proteins Vif and Vpu to usurp cellular ubiquitin ligases for viral functions...
- Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular developmentRyosuke Tsunematsu
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
J Biol Chem 279:9417-23. 2004..Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7(-/-) embryos. Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development...
- Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RINGAllan D Capili
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
J Mol Biol 340:1117-29. 2004..From a comparison of the RING2 structure with those reported for RINGs, we infer sequence determinants that allow discrimination between RING2 and RING domains at the sequence analysis level...
- Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responsesS I Matsuzawa
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell 7:915-26. 2001..Expression of Siah is induced by p53, revealing a way of linking genotoxic injury to destruction of beta-catenin, thus reducing activity of Tcf/LEF transcription factors and contributing to cell cycle arrest...
- Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligaseY Zhang
Laboratory of Cellular and Molecular Biology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 98:974-9. 2001....
- De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndromeT Matsuura
Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
Nat Genet 15:74-7. 1997..It may represent an example of a human genetic disorder associated with a locus producing functionally distinct imprinted and biallelically expressed gene products...
- The disruption of ND10 during herpes simplex virus infection correlates with the Vmw110- and proteasome-dependent loss of several PML isoformsR D Everett
MRC Virology Unit, Glasgow G11 5JR, Scotland
J Virol 72:6581-91. 1998..These observations provide a biochemical mechanism to explain the observed effects of Vmw110 on ND10 and suggest a simple yet powerful mechanism by which Vmw110 might function during virus infection...
- Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitroNoriyuki Matsuda
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613
J Biol Chem 281:3204-9. 2006....
- Whose end is destruction: cell division and the anaphase-promoting complexW Zachariae
Research Institute of Molecular Pathology, A 1030 Vienna, Austria
Genes Dev 13:2039-58. 1999
- Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-bK Bachmaier
Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada
Nature 403:211-6. 2000..Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity...
- The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptorAndrea Vecchione
Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Mol Cell Biol 23:3363-72. 2003..This is the first demonstration of regulation of stability of a tyrosine kinase receptor by the Nedd4 (HECT) family of E3 ligases...
- Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkinVentzislava A Hristova
Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
J Biol Chem 284:14978-86. 2009..The identification of the RING0 domain in parkin provides a new overall domain structure for the protein that will be important in assessing the roles of ARJP mutations and designing experiments aimed at understanding the disease...
- Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5Joanne L Parker
Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Herts, UK
EMBO J 28:3657-66. 2009..Our results provide information about a unique conjugation mechanism that appears to be specialised for a regulatable pattern of dual modification...
- Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to CellsLAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012..Understanding more precisely the characteristics of and the mechanism(s) behind desensitization will enable physicians to better utilize this approach to reduce mast cell/basophil-mediated contributions to asthma and allergic diseases. ..
- REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASESMelanie H Cobb; Fiscal Year: 2012..Understanding the mechanisms of action of this family will provide significant insights into the control of ion balance and other essential processes, and may reveal novel strategies to develop anti-hypertensive therapies. ..
- Induction and maintenance of regulatory T cellsMitchell Kronenberg; Fiscal Year: 2013..This proposal will study the mechanisms by which the immune responses are properly controlled. Such knowledge will eventually facilitate the design of novel therapeutic approaches for immunological diseases. ..
- Cell Cycle Regulation and Adult T Cell LeukemiaChou Zen Giam; Fiscal Year: 2013..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
- Diverse Roles for RIC8 During G Protein Signaling in FungiKatherine A Borkovich; Fiscal Year: 2012....
- Hepatitis B virus replication and DDB1Betty L Slagle; Fiscal Year: 2013..This important new knowledge will reveal virus-induced changes at the post-translational level, and is predicted to provide mechanistic insight into new strategies through which to treat chronic HBV infection and prevent liver disease. ..
- Molecular Pathological Mechanism & Potential Therapeutics of Lafora DiseaseYAN NONE LIU; Fiscal Year: 2010..Knowledge gained from this project could greatly improve the care of Lafora patients and provide very important insight for developing therapeutic agents for the treatment of the so far incurable LD patients. ..
- Molecular Pathogenesis of MDS and CMMLJaroslaw P Maciejewski; Fiscal Year: 2013..We will precisely map these lesions, identifying genes that may play a role in the disease and potentially act as targets of therapy. ..
- Role of inflammation and cellular stress in the pathogenesis of type 2 diabetesLiangyou Rui; Fiscal Year: 2013..The outcome is expected to lead to new therapies for hepatic steatosis and type 2 diabetes by targeting the NIK pathways. ..
- Misregulation of receptor tyrosine kinase signaling in PKDJordan A Kreidberg; Fiscal Year: 2013..Failure to ubquitinate c-Met is due to sequestration of the E3 ubiquitin ligase c-Cbl by 31 integrin in the Golgi apparatus. This grant will investigate the roles of c-Cbl, c-Met and protein glycosylation in the pathogenesis of PKD. ..
- Genetic Control of Axial Patterning in Drosophila EyeAmit Singh; Fiscal Year: 2010..It will also help to understand the molecular basis of developmental defects caused by mutations in the human homolog of Drosophila. ..
- Post-translational regulation of MLL in leukemogenesisANDREW GEORGE MUNTEAN; Fiscal Year: 2013..These studies focus on the MLL-PAFc interaction and ubiquitination of MLL which are directly relevant to MLL and HOX dependent leukemias and may prove as effective therapeutic targets. ..
- Post-translational regulation of MLL in leukemogenesisANDREW GEORGE MUNTEAN; Fiscal Year: 2012..These studies focus on the MLL-PAFc interaction and ubiquitination of MLL which are directly relevant to MLL and HOX dependent leukemias and may prove as effective therapeutic targets. ..
- The Role of hPso4 in DNA Repair and Chemotherapy ResistanceMontaser Shaheen; Fiscal Year: 2013..We will deplete this E2 and evaluate if this will achieve the same chemosensitivity as depleting hPso4. This will open the opportunity to identify Ubc3 small molecule inhibitors as cancer therapy. ..
- REGULATION OF NUCLEAR ENVELOPE ASSEMBLY AND DISASSEMBLYKatherine L Wilson; Fiscal Year: 2012..Aim 3 is a whole-genome and promoter-specific analysis of BAF function in C. elegans, which is expected to identify genes relevant to its roles in muscle and DNA- damage responses. ..
- Mechanisms of cancer initiation by TRIM32Molly F Kulesz-Martin; Fiscal Year: 2012..abstract_text> ..
- Molecular and Cellular Mechanisms of IL-17 SignalingXiaoxia Li; Fiscal Year: 2013....
- Negative regulation of NF-kB and inflammation by TAX1BP1Edward W Harhaj; Fiscal Year: 2012..This proposal will provide mechanistic insight into how TAX1BP1, Itch and A20 function together to inactivate key signaling molecules and restrict inflammatory signaling pathways. ..
- Analysis of NKLAM: A Novel Gene Associated With Cellular CytotoxicityJacki Kornbluth; Fiscal Year: 2013..A variety of tumor models will be evaluated to determine where NKLAM plays a role. Analysis of NKLAM KO mice may reveal additional roles for NKLAM and potentially unveil alternative mechanisms of cell killing. ..
- Spinocerebellar Ataxia Type 2 Gene and Gene ProductStefan M Pulst; Fiscal Year: 2012..This will allow us to test the effects of specific proteins on nerve cell dysfunction and cell death in live animals with the ultimate goal of identifying new therapeutic avenues for treatment of human neurodegenerative diseases. ..
- Characterizaton of Motility Factor ReceptorAvraham Raz; Fiscal Year: 2012..It is expected that these studies will lead to a better diagnosis, treatment and development of rational therapy. ..
- Meiosis, SUMOylation and the ZIP3 Protein: Parallel Studies in Mouse and Yeast.Neil Hunter; Fiscal Year: 2012..Defects in these processes are linked to human infertility, miscarriage and genetic diseases, particularly cancer. A greater understanding of their mechanism and regulation will help us better understand the etiology of these diseases. ..
- Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer FunctiJacki Kornbluth; Fiscal Year: 2010..These diseases are of great relevance to the health care system as the incidence of cancer is rising as the population is aging and new, resistant microbial pathogens are emerging and spreading. ..
- Mechanistic validation of SCF E3 ligase as a cancer and radiosensitizing targetYi Sun; Fiscal Year: 2013..This study will validate SCF E3 ubiquitin ligase as an anticancer and radiosensitizing target and MLN4924, a newly discovered SCF E3 ligase inhibitor, as a tumor-selective and radiosensitizing agent for cancer therapy. ..
- Training/Research Center-Bone Marrow Failure SyndromesJaroslaw P Maciejewski; Fiscal Year: 2013..We will precisely map these lesions, identifying genes that may play a role in the disease and potentially act as targets of therapy;these studies will form the basis for the training program proposed. ..
- HTLV-I Tax activates the anaphase promoting complexChou Zen Giam; Fiscal Year: 2013..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
- Inflammatory Cytokines Link NF-kappaB with Bim Degradation and MetastasisMarty W Mayo; Fiscal Year: 2012..Understanding the mechanisms used by inflammatory mediators to stimulate Bim degradation will potentially result in the identification of novel approaches to preventing NSCLC metastasis. ..
- Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte DeathAbdelkarim Sabri; Fiscal Year: 2012....
- Elucidating the in vivo Role of the p53 Apoptosis-Specific Target Gene SivaJeanine L Frey; Fiscal Year: 2013..abstract_text> ..
- Novel Strategies for Treatment of Myeloproliferative DisordersRoya Khosravi-Far; Fiscal Year: 2012..abstract_text> ..
- Regulation of Osteoblast Function by Megakaryocytes: Key Signaling ProteinsMelissa A Kacena; Fiscal Year: 2013..Identifying the pathways that lead to enhanced bone volume in vivo will lead to the development of novel therapeutic approaches that stimulate bone formation for the treatment of osteoporosis and other bone loss diseases. ..
- HoxA10 Function During Myeloid DifferentiationELIZABETH ANN EKLUND; Fiscal Year: 2011..Therefore, the goal of these studies is to identify novel targets for the treatment of myeloid malignancy. ..
- Modulating calcineurin signaling pathways in muscleBeverly A Rothermel; Fiscal Year: 2012..abstract_text> ..
- Regulation and Role of Ornithine Decarboxylase in Cell Proliferation and CancerJohn L Cleveland; Fiscal Year: 2013..abstract_text> ..
- Regulation of Hepatic Carbohydrate Metabolism by STBD1Alan Cheng; Fiscal Year: 2012..Importantly, this can ultimately identify novel therapeutic avenues in these diseases. ' ..
- Characterization of TGR5-D2-WSB1 signaling in metabolic homeostasis in vivoANTONIO C contact BIANCO; Fiscal Year: 2010..2. Tissue-specific TGR5 and WSB1 expression is critical in metabolic control. 3. Signaling through the TGR5-D2-WSB1 pathway affects cellular metabolic profile and gene expression profiles. ..
- CONTROL OF APOPTOSIS BY DROSOPHILA CELL DEATH GENESHermann Steller; Fiscal Year: 2012..Therefore, this project will have profound implications for both basic science and medicine. ..
- Role of Parkin in Regulating Manganese ToxicityJEROME ALLAN ROTH; Fiscal Year: 2010..Thus, the studies proposed in this grant are relevant to human health in that they will investigate the mechanism by which mutations in the parkin gene regulate and increase vulnerability to develop manganism. ..
- Novel Model Systems Link Floridean Starch Metabolism to Lafora DiseaseMatthew S Gentry; Fiscal Year: 2010..The findings from all three of my specific aims can be applied to identify new therapeutic targets to treat LD and possibly other polyglucosan diseases. ..
- Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolismLei Yin; Fiscal Year: 2009..In addition, this work may shed the new light on identifying new therapeutic targets for treating insulin resistance and diabetes. ..
- Biology of nuclear receptor rev-erb alpha in circadian rhythm and metabolismLei Yin; Fiscal Year: 2011..In addition, this work may shed the new light on Identifying the new therapeutic targets for treating Insulin resistance and diabetes. ..
- Secretory Vesicle Function During Spermatogenesis & Fertilization in C. elegansSTEVEN W L apos HERNAULT; Fiscal Year: 2010..The processes we study, in addition to functioning in sperm, also play a role in proper kidney function and bone formation. ..
- NUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESISPETER J TONTONOZ; Fiscal Year: 2013..We will also generate and analyze lesion formation in Idol-/- human apoBTg mice. ..
- The Role of the Cochaperone/E3 Ubiquitin Ligase CHIP in Nuclear Stress ResponseSARAH MARIE RONNEBAUM; Fiscal Year: 2010....
- Rest-Activated Program of Gene Expression in IschemiaR Suzanne Zukin; Fiscal Year: 2013....
- Regulation of SMN and Identification of its Downstream TargetJudith Jebanathirajah Steen; Fiscal Year: 2013..abstract_text> ..
- Study of an iron-responsive E3 ligase regulating mammalian iron homeostasisRichard K Bruick; Fiscal Year: 2013..To that end, this proposal describes the characterization of a candidate sensor and regulator of mammalian iron homeostasis, FBXL5. ..
- REGULATION OF DEFENSE SIGNALING IN TOMATOGregg A Howe; Fiscal Year: 2012....
- Enhancement of Medullary Erythropoiesis during Anemia by Trib3David Kuhrt; Fiscal Year: 2013..This trainin plan is designed to advance impacting first author papers and expertise as a new independent investigator. ..
- Programmed Cell Death and Disease Resistance in ArabidopsisRoger W Innes; Fiscal Year: 2013..Together with Specific Aims 1-3, these analyses will provide significant new insight into how PCD and immunity are regulated. ..
- Host-pathogen competition in IFN mediated antiviral defenseJae U Jung; Fiscal Year: 2013....
- Ubiquitin-like protein modification in diabetic cardiomyopathyJay Yang; Fiscal Year: 2013..The significance lies in the novel hypothesis on the role of the Ub-ligase CHIP in regulating both apoptosis and autophagy, and the proposed mechanistic study of a highly clinically relevant problem. ..
- FLUID SHEAR STRESS SIGNAL TRANSDUCTION IN ENDOTHELIUMKeigi Fujiwara; Fiscal Year: 2013..Elucidating the specific pathways by which protein kinase C-zeta modulates vessel function would provide the basis to develop new therapies to prevent atherosclerosis. ..
- Mechanism of Gli3 processing in Hedgehog signalingBaolin Wang; Fiscal Year: 2013..The completion of the proposed studies will significantly advance our understanding of the regulation and function of Gli3 protein in Hh signaling. ..
- CARP-1: A Potential Therapeutic Agent for Breast CancerARUN KUMAR RISHI; Fiscal Year: 2013..abstract_text> ..
- Asb2 in CD4+ T cell lineage differentiation and its plasticityXiao Hong Sun; Fiscal Year: 2013..Fresh ideas will likely emerge from these studies that will be o therapeutic value in the contest of immunity and autoimmunity. ..
- Hypoxia and Anticancer Drug ActionGarth Powis; Fiscal Year: 2013..abstract_text> ..
- Trim32 Regulation of Piasy in Skin HomeostasisMolly F Kulesz-Martin; Fiscal Year: 2013..Ultimately, these studies may impact our understanding of the molecular mechanisms of psoriasis as distinct from atopic dermatitis and lead to rational improvement of treatment strategies for psoriasis patients. ..
- FINR: A Novel Modulator of Insulin SignalingMarc R Montminy; Fiscal Year: 2010..The current proposal focuses on the role of a so- called insulin resistance protein called TRB3 in preventing the insulin signal from working in muscle and other tissues in the body. ..
- Indolecarbinol target proteins and anti-cancer signaling in human melanoma cellsGary L Firestone; Fiscal Year: 2013..Our proposed studies will establish the preclinical foundation that is needed to eventually develop novel and low cost I3C-based therapeutic strategies for human skin cancers. ..
- Assembly and Trafficking of IK1 and SK3 in EndotheliaDaniel C Devor; Fiscal Year: 2012..Our studies will provide novel insight into how these processes can be manipulated for clinical gain. ..
- A Novel Carcinogen-Induced Cell Cycle CheckpointCyrus Vaziri; Fiscal Year: 2013..g. Rad18 or its activating kinases) whose inhibition enhances the efficacy of existing cancer therapies. ..
- Quantitative Analysis of RING E3 Ubiquitin LigasesCHARLES M BRENNER; Fiscal Year: 2010..Second, innovations in analysis of RING E3 ubiquitin ligases are necessary to understand the specificity of function of RING E3 ubiquitin ligases, which have key functions in the health of every organ system. ..
- TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESISBryant G Darnay; Fiscal Year: 2010..In particular, the data gathered from these experiments may provide insights to developing therapeutic strategies for a variety of bone related disease and possibly other diseases associated with immunity and inflammation ..
- Roles of ubiquitin protein ligases in endocytosisLinda Hicke; Fiscal Year: 2005..b>Ubiquitin protein ligases are key components of the ubiquitination machinery that recognize and modify specific plasma membrane ..
- MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DEHui Zhang; Fiscal Year: 2001..These studies should also provide a basis to design novel strategies for diagnosis, prognosis, and therapeutic treatment of breast cancers. ..
- Salmonella SopA is a functional mimicry of eukaryotic E3 protein ubiquitin ligaseDaoguo Zhou; Fiscal Year: 2010..Results from this study will help us understand how Salmonella induces intestinal inflammation in humans. ..
- Capture of Ubiquitin Conjugation and Deconjugation Enzyme SubstratesRobert Cohen; Fiscal Year: 2010..To overcome this problem, a new approach termed cognate-complex biotin tagging ("CBiT") will be developed and applied to complexes that regulate ubiquitin-dependent signaling. ..
- Luciferase Screen for MDM2 E3 Ligase InhibitorsBrent Stockwell; Fiscal Year: 2007..In addition, small molecules can sometimes be developed into therapeutic agents. In this application, we propose to screen for small molecules that inhibit MDM2 E3 ligase activity. [unreadable] [unreadable] [unreadable]..
- Novel Small Molecule Inhibitors of HIVXiao Fang Yu; Fiscal Year: 2010..We have identified a small molecule inhibitor of Vif. The overall goal of this project is to further characterize the novel small molecule Vif inhibitor and its derivatives that restore the potent innate antiviral defense. ..