title: HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation.
abstract: MyoD is a tissue-specific transcriptional activator that acts as a master switch for muscle development. It activates a broad array of muscle-specific genes, which leads to conversion of proliferating myoblasts into mature myotubes. The ubiquitin proteasome system (UPS) plays an important role in controlling MyoD. Both its N-terminal residue and internal lysines can be targeted by ubiquitin, and both modifications appear to direct it for proteasomal degradation. The protein is short-lived and has a half-life of ∼45min in different cells. It was reported that MyoD can be ubiquitinated by MAFbx/AT-1, but accumulating lines of experimental evidence showed that other ligase(s) may also participate in its targeting. Here we describe the involvement of HUWE1 in the ubiquitination and proteasomal degradation of MyoD. Furthermore, we show that the ligase can ubiquitinate the protein in its N-terminal residue.
authors.affiliation: Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Tahel
authors.initials: T
authors.lastname: Noy
authors.forename: Oded
authors.initials: O
authors.lastname: Suad
authors.forename: Daniel
authors.initials: D
authors.lastname: Taglicht
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
mesh_terms: D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D017570:MyoD Protein / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D017570:MyoD Protein; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C502830:HUWE1 protein, human; C115246:TOM1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex