title: Cops2 promotes pluripotency maintenance by Stabilizing Nanog Protein and Repressing Transcription.
abstract: The COP9 signalosome has been implicated in pluripotency maintenance of human embryonic stem cells. Yet, the mechanism for the COP9 signalosome to regulate pluripotency remains elusive. Through knocking down individual COP9 subunits, we demonstrate that Cops2, but not the whole COP9 signalosome, is essential for pluripotency maintenance in mouse embryonic stem cells. Down-regulation of Cops2 leads to reduced expression of pluripotency genes, slower proliferation rate, G2/M cell cycle arrest, and compromised embryoid differentiation of embryonic stem cells. Cops2 also facilitates somatic cell reprogramming. We further show that Cops2 binds to Nanog protein and prevent the degradation of Nanog by proteasome. Moreover, Cops2 functions as transcriptional corepressor to facilitate pluripotency maintenance. Altogether, our data reveal the essential role and novel mechanisms of Cops2 in pluripotency maintenance.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Peiling
authors.initials: P
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Mou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.|State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.|Epigenetics and Cell Fates Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Epigenetics and Cell Fates Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Yuin-Han
authors.initials: YH
authors.lastname: Loh
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.|State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000075686:COP9 Signalosome Complex / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000066673:Cell Self Renewal; D000067470:Cellular Reprogramming Techniques; D058732:Embryoid Bodies; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D055550:Protein Stability; D059748:Proteolysis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D055751:SOXC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D012756:Sheep / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: C118919:Cops2 protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D014157:Transcription Factors; D000075686:COP9 Signalosome Complex