title: Ubiquitin-specific protease 21 regulating the K48-linked polyubiquitination of NANOG.
abstract: NANOG, one of homeobox proteins, plays a crucial role in regulating self-renewal and pluripotency for embryonic stem cells (ESCs). Since the ubiquitin-mediated degradation of NANOG protein has been implicated in its cellular functions involved in not only maintenance of pluripotency and pluripotent epiblast, but also prevention of primitive endoderm differentiation, the identification of ubiquitin ligases and deubiquitinating enzymes (DUBs) for NANOG is required to elucidate its protein stability and the regulation of cellular functions in these processes. In this study, we have identified a novel deubiquitinating enzyme USP21 which interacts with NANOG by both yeast two hybrid screening for DUBs and immunoprecipitation analyses. These analyses revealed that USP21 specifically regulates the Lys48-linked polyubiquitination and stability of NANOG, providing a new way of maintaining the pluripotency of ESCs and induced pluripotent stem cells (iPSCs).
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea.
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea.
authors.forename: Da-Hye
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do, 13488, Republic of Korea. Electronic address: baek@cha.ac.kr.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D005982:Glutathione Transferase / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000737:chemistry*; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C408875:USP21 protein, human; D025801:Ubiquitin; D005982:Glutathione Transferase; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D008239:Lysine
keywords: Deubiquitination; Differentiation; Pluripotency; Proteasomal degradation; Stem cell; Ubiquitination