Genomes and Genes
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
- The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasisZhenyue 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. 2012Cellular 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...
- Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histonesZhiqian 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...
- ARF-BP1/Mule is a critical mediator of the ARF tumor suppressorDelin 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...
- 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..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...
- Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in miceNing 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...
- The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoproteinXudong 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 ..
- E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alphaLei 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...
- miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cellsBo 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...
- Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYCChen 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. ..
- Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditionsLinyuan 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...
- Syk-mediated tyrosine phosphorylation of mule promotes TNF-induced JNK activation and cell deathC 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...
- A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiationLi 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...
- Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal DegradationCarmen 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. 2016The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown...
- Return to quiescence of mouse neural stem cells by degradation of a proactivation proteinNoelia 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 ..
- Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2Jing 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...
- Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15Satoshi 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...
- Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cellsCatherine 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...
- Characterization of ARF-BP1/HUWE1 interactions with CTCF, MYC, ARF and p53 in MYC-driven B cell neoplasmsChen 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 ..
- Regulation of oxidative DNA damage repair by DNA polymerase λ and MutYH by cross-talk of phosphorylation and ubiquitinationEnni 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 ..
- Chromosomal domains and escape from X inactivation: comparative X inactivation analysis in mouse and humanK 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...
- Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding siteMatthew 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...
- USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1Xinna 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...
- E3 ubiquitin ligase Mule ubiquitinates Miz1 and is required for TNFalpha-induced JNK activationYi 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...
- Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellumDomenico 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. 2010We 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...
- The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brainXudong 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...
- Regulated expression of the ubiquitin protein ligase, E3(Histone)/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesisZhiqian Liu
Department of Biochemistry, McGill University, Montreal, Quebec, Canada
Dev Dyn 236:2889-98. 2007A 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...
- Ribosomal protein L12 uses a distinct nuclear import pathway mediated by importin 11Scott 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...