title: Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction.
abstract: Itch, a C2-WW-HECT domain ubiquitin E3 ligase, plays an important role in various biological processes. However, its role in embryonic stem cells (ESCs) remains unknown. Here, we report that Itch interacts with and targets pluripotency-associated transcription factor Oct4 for ubiquitination. Moreover, Itch enhances Oct4 transcriptional activities and controls Oct4 protein stability dependent on its catalytic activity. Importantly, silencing Itch expression compromises ESC self-renewal capacity and somatic cell reprogramming efficiency. Taken together, our study identifies Itch as a regulator of Oct4 stability and transcriptional activity, establishing a functional link between an E3 ligase and the regulation of pluripotency.
authors.affiliation: Shanghai Stem Cell Institute, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhong
authors.forename: Huiming
authors.initials: H
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.forename: Zhuoqing
authors.initials: Z
authors.lastname: Fang
authors.forename: Junjie
authors.initials: J
authors.lastname: Gu
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D002460:Cell Line; D049109:Cell Proliferation; D054278:Embryonal Carcinoma Stem Cells; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; C432966:ITCH protein, human; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases