title: Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during senescence.
abstract: The inhibitor of differentiation or DNA binding (Id) family of transcription regulators plays an important role in cell proliferation, differentiation, and senescence. However, regulation of Id expression during these processes is poorly understood. Id proteins are known to undergo rapid turnover mediated by the ubiquitin-proteasome pathway. Anaphase-promoting complex has been shown to ubiquitinate Id2, but E3 ubiquitin ligase(s) that ubiquitinate other Id family members are not known. Here, we report for the first time the identification of Smurf2 as the E3 ligase that ubiquitinates Id1 and Id3. Smurf2-mediated ubiquitination and consequent degradation of Id1 or Id3 plays an important role in the regulation of Id expression in senescent cells. Furthermore, we found that Id1 is the mediator through which Smurf2 regulates p16 expression, providing a mechanistic link between Smurf2 and p16 expression during senescence.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Kong
authors.forename: Hang
authors.initials: H
authors.lastname: Cui
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D025801:Ubiquitin; C075640:ID3 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; C471641:SMURF2 protein, human; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases