Huwe1

Summary

Gene Symbol: Huwe1
Description: HECT, UBA and WWE domain containing 1
Alias: 5430439H10Rik, AU041296, Arf-bp1, C430014N20Rik, C80292, Gm1718, Ib772, LASU1, Mule, Ureb1, E3 ubiquitin-protein ligase HUWE1, E3Histone, HECT, UBA and WWE domain-containing protein 1, HECT-type E3 ubiquitin transferase HUWE1, Mcl-1 ubiquitin ligase, URE-B1, URE-binding protein 1, upstream regulatory element binding protein 1
Species: mouse

Top Publications

  1. pmc The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis
    Zhenyue Hao
    The Campbell Family Institute for Cancer Research and 2 Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    J Exp Med 209:173-86. 2012
  2. pmc Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones
    Zhiqian Liu
    Polypeptide Hormone Laboratory, McGill University, Strathcona Anatomy and Dentistry Building, 3640 University St, Room W315, Montreal, Quebec, Canada, H3A 2B2
    Mol Cell Biol 25:2819-31. 2005
  3. ncbi ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor
    Delin Chen
    Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, New York 10032
    Cell 121:1071-83. 2005
  4. ncbi Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis
    Qing Zhong
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    Cell 121:1085-95. 2005
  5. pmc Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice
    Ning Kon
    Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 287:5102-11. 2012
  6. pmc The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein
    Xudong Zhao
    Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA
    Nat Cell Biol 10:643-53. 2008
  7. pmc E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha
    Lei Yin
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 107:11614-9. 2010
  8. pmc miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells
    Bo Xu
    1 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China 2 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China 3 Department of Endocrinology, The Affiliated Jiangyin Hospital of Wuxi Clinical School of Medicine, Nanjing Medical University, Jiangyin 214400, China
    Sci Rep 5:12938. 2015
  9. pmc Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYC
    Chen Feng Qi
    Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States Electronic address
    Leuk Res 37:1680-9. 2013
  10. doi Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions
    Linyuan Wang
    Toronto General Research Institute, University Health Network, MaRS Ctre, TMDT, 101 College St, 10th Floor, Rm 10 363, Toronto, ON, Canada, M5G 1L7
    Diabetologia 57:1889-98. 2014

Scientific Experts

  • Chen Feng Qi
  • Zhenyue Hao
  • Catherine Corbel
  • S M Plafker
  • Lei Yin
  • Tak W Mak
  • Xudong Zhao
  • Carmen Dominguez-Brauer
  • Satoshi Inoue
  • Zhiqian Liu
  • Francois Guillemot
  • Ning Kon
  • Antonio Iavarone
  • Anna Lasorella
  • Noelia Urbán
  • C K Lee
  • Qing Zhong
  • Bo Xu
  • Li Li
  • Andrew Wakeham
  • Jennifer Silvester
  • Andrew J Elia
  • Jillian Haight
  • Iok In Christine Chio
  • Linyuan Wang
  • Enni Markkanen
  • Xinna Zhang
  • Matthew R Warr
  • Jing Zhang
  • Domenico D'Arca
  • Yi Yang
  • Wei Gu
  • Simon S Wing
  • Delin Chen
  • Miyeko D Mana
  • Debbie L C van den Berg
  • Antoine Forget
  • Aaron Pollett
  • Jeroen A A Demmers
  • Leanne Tworzyanski
  • Jerome M Fortin
  • Y Yang
  • Hans Clevers
  • Yi Sheng
  • Toshiro Sato
  • Johan H van Es
  • Charles Hunt
  • David M Sabatini
  • C Chen
  • Ana Marques
  • Olivier Ayrault
  • Colin Reardon
  • ROBERT CAIRNS
  • Jimena Andersen
  • Omer H Yilmaz
  • J Liu
  • Patrick M Brauer
  • Robert Nechanitzky
  • Maureen A Cox
  • Qiusha Tang
  • Xiaoli Ji
  • Silvia Sanchez Martinez
  • Zhe Liu
  • Yi Liu
  • Minjian Chen
  • Mengmeng Yao
  • Bo Hang
  • Yankai Xia
  • Xuemei Zhang
  • Wenxin Hu
  • Robert Tjian
  • Zhilei Mao
  • Wei Tang
  • Alannah M Smith
  • Minna Woo
  • Xie Li
  • Herbert Gaisano
  • Cynthia T Luk
  • Erica P Cai
  • Patrick E MacDonald
  • Stephanie A Schroer
  • Kazuo Yamamoto
  • Danny Ghazarian
  • Momoe Itsumi
  • Bryan Snow
  • Linda J Z Penn
  • David Cescon
  • Isaac S Harris
  • Lily Zhou
  • Gerry Melino

Detail Information

Publications27

  1. pmc The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis
    Zhenyue Hao
    The Campbell Family Institute for Cancer Research and 2 Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    J Exp Med 209:173-86. 2012
    Cellular homeostasis is controlled by pathways that balance cell death with survival. Mcl-1 ubiquitin ligase E3 (Mule) is an E3 ubiquitin ligase that targets the proapoptotic molecule p53 for polyubiquitination and degradation...
  2. pmc Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones
    Zhiqian Liu
    Polypeptide Hormone Laboratory, McGill University, Strathcona Anatomy and Dentistry Building, 3640 University St, Room W315, Montreal, Quebec, Canada, H3A 2B2
    Mol Cell Biol 25:2819-31. 2005
    ..Indeed, a novel enzyme, E3Histone, which could conjugate ubiquitin to histones H1, H2A, H2B, H3, and H4 in vitro, was found...
  3. ncbi ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor
    Delin Chen
    Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, New York 10032
    Cell 121:1071-83. 2005
    ..As such, ARF-BP1 may serve as a potential target for therapeutic intervention in tumors regardless of p53 status...
  4. ncbi Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis
    Qing Zhong
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    Cell 121:1085-95. 2005
    ..fractionation of cell extracts allowed us to identify a 482 kDa HECT-domain-containing ubiquitin ligase named Mule (Mcl-1 ubiquitin ligase E3) that is both required and sufficient for the polyubiquitination of Mcl-1...
  5. pmc Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice
    Ning Kon
    Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 287:5102-11. 2012
    ..These findings underscore an important role of ARF-BP1 in maintaining β-cell homeostasis in aging mice and reveal that the stability of p53 is critically regulated by ARF-BP1 in vivo...
  6. pmc The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein
    Xudong Zhao
    Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA
    Nat Cell Biol 10:643-53. 2008
    ..Here we report that the HECT-domain ubiquitin ligase Huwe1 ubiquitinates the N-Myc oncoprotein through Lys 48-mediated linkages and targets it for destruction by the ..
  7. pmc E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha
    Lei Yin
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 107:11614-9. 2010
    ..Thus, Arf-bp1 and Pam are novel regulators of circadian gene expression that target Rev-erb alpha for degradation...
  8. pmc miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells
    Bo Xu
    1 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China 2 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China 3 Department of Endocrinology, The Affiliated Jiangyin Hospital of Wuxi Clinical School of Medicine, Nanjing Medical University, Jiangyin 214400, China
    Sci Rep 5:12938. 2015
    ..Accordingly, the expression level of miR-98, which can regulate Caspase-3, was significantly decreased. Huwe1, the host gene of miR-98, was positively associated with miR-98 expression after Silica NP exposure...
  9. pmc Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYC
    Chen Feng Qi
    Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States Electronic address
    Leuk Res 37:1680-9. 2013
    ..These findings indicate that the dynamic balance between MYC and p53 required for normal B cell maturation and function is finely tuned and critically dependent on the activities of ARF-BP1. ..
  10. doi Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions
    Linyuan Wang
    Toronto General Research Institute, University Health Network, MaRS Ctre, TMDT, 101 College St, 10th Floor, Rm 10 363, Toronto, ON, Canada, M5G 1L7
    Diabetologia 57:1889-98. 2014
    ..A newly discovered ubiquitination molecule HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1 [also known as MULE or ARF-BP1]) is a critical regulator of p53-dependent apoptosis...
  11. pmc Syk-mediated tyrosine phosphorylation of mule promotes TNF-induced JNK activation and cell death
    C K Lee
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Oncogene 35:1988-95. 2016
    ..and cell death by suppressing TRAF2 K63-polyubiquitination; upon TNF stimulation, the suppression is relieved by Mule/ARF-BP1-mediated Miz1 ubiquitination and subsequent degradation. It is not known how Mule is activated by TNF...
  12. pmc A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation
    Li Li
    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    elife 4:e08536. 2015
    ..Using an in vitro ubiquitination assay coupled with biochemical fractionation, we identified Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation...
  13. pmc Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation
    Carmen Dominguez-Brauer
    The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada
    Cell Stem Cell 19:205-16. 2016
    The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown...
  14. pmc Return to quiescence of mouse neural stem cells by degradation of a proactivation protein
    Noelia Urbán
    The Francis Crick Institute Mill Hill Laboratory, NW7 1AA, London, UK
    Science 353:292-5. 2016
    ..Here, we show that the E3-ubiquitin ligase Huwe1 (HECT, UBA, and WWE domain-containing 1) is required for proliferating stem cells of the adult mouse hippocampus ..
  15. pmc Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2
    Jing Zhang
    Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Genes Dev 25:2610-8. 2011
    ..apoptosis are severely compromised in mouse embryonic fibroblasts lacking a HECT domain ubiquitin ligase, Mule (Mcl-1 ubiquitin ligase E3). Mule specifically targets HDAC2 for ubiquitination and degradation...
  16. pmc Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15
    Satoshi Inoue
    The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2C1, Canada
    Genes Dev 27:1101-14. 2013
    ..Many gene products involved in these processes are substrates of the E3 ubiquitin ligase Mule/Huwe1/Arf-BP1 (Mule), but whether Mule acts as an oncogene or tumor suppressor in vivo remains controversial...
  17. doi Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cells
    Catherine Corbel
    Unité de génétique et biologie du développement, Institut Curie, CNRS UMR 3215, INSERM U934, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Development 140:861-72. 2013
    ..This unusual combination of silent and active features is likely to reflect, and might underlie, the partial activity of the X chromosome in TGCs...
  18. pmc Characterization of ARF-BP1/HUWE1 interactions with CTCF, MYC, ARF and p53 in MYC-driven B cell neoplasms
    Chen Feng Qi
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA E Mails Y S K S X Z A A L K J S
    Int J Mol Sci 13:6204-19. 2012
    ..The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is ..
  19. pmc Regulation of oxidative DNA damage repair by DNA polymerase λ and MutYH by cross-talk of phosphorylation and ubiquitination
    Enni Markkanen
    Institute for Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 109:437-42. 2012
    ..Here, we show that the E3 ligase Mule mediates the degradation of Pol λ and that the control of Pol λ levels by Mule has functional consequences for ..
  20. ncbi Chromosomal domains and escape from X inactivation: comparative X inactivation analysis in mouse and human
    K D Tsuchiya
    Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, Ohio 44106 4955, USA
    Mamm Genome 11:849-54. 2000
    ..Possible mechanisms responsible for the differing inactivation status between genes in the escape domain in human Xp11. 21-p11.22 and the corresponding mouse region are discussed...
  21. pmc Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site
    Matthew R Warr
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 286:25098-107. 2011
    ..outer membrane, is subject to constitutive ubiquitylation by the Bcl-2 homology 3-only E3 ligase, Mule/Lasu1, resulting in rapid steady-state degradation via the proteasome...
  22. pmc USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1
    Xinna Zhang
    Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
    EMBO J 30:2177-89. 2011
    ..Finally, we showed that USP4 is overexpressed in several types of human cancer, suggesting that USP4 is a potential oncogene...
  23. pmc E3 ubiquitin ligase Mule ubiquitinates Miz1 and is required for TNFalpha-induced JNK activation
    Yi Yang
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 107:13444-9. 2010
    ..However, the underling regulatory mechanism is not known. Here, we report that HECT-domain-containing Mule is the E3 ligase that catalyzes TNFalpha-induced Miz1 polyubiquitination...
  24. pmc Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellum
    Domenico D'Arca
    Department of Pathology, Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:5875-80. 2010
    We have generated a knockout mouse strain in which the gene coding for the ubiquitin ligase Huwe1 has been inactivated in cerebellar granule neuron precursors (CGNPs) and radial glia...
  25. pmc The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain
    Xudong Zhao
    Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA
    Dev Cell 17:210-21. 2009
    ..Here we show that the ubiquitin ligase Huwe1 operates upstream of the N-Myc-DLL3-Notch pathway to control neural stem cell activity and promote neurogenesis...
  26. ncbi Regulated expression of the ubiquitin protein ligase, E3(Histone)/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesis
    Zhiqian Liu
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Dev Dyn 236:2889-98. 2007
    A ubiquitin protein ligase (E3), E3(Histone)/LASU1 (Mule/ARF-BP1/HUWE1), was recently identified that mediates ubiquitination of core histones, the Mcl-1 anti-apoptotic protein, and the p53 tumor suppressor protein...
  27. pmc Ribosomal protein L12 uses a distinct nuclear import pathway mediated by importin 11
    Scott M Plafker
    Center for Cell Signaling and Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA
    Mol Cell Biol 22:1266-75. 2002
    ..Taken together, these results indicate that rpL12 uses a distinct nuclear import pathway that may contribute to a mechanism for regulating ribosome synthesis and/or maturation...