Cited 92 times in
Role of cdk2 in the sequential phosphorylation/activation of C/EBPβ during adipocyte differentiation
DC Field | Value | Language |
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dc.contributor.author | 김재우 | - |
dc.date.accessioned | 2014-12-21T17:17:42Z | - |
dc.date.available | 2014-12-21T17:17:42Z | - |
dc.date.issued | 2007 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/97318 | - |
dc.description.abstract | Upon induction of differentiation, growth-arrested (G1 phase) 3T3-L1 preadipocytes express CCAAT/enhancer binding protein-β (C/EBPβ), initiating a transcriptional cascade. C/EBPβ immediately undergoes a priming phosphorylation (on Thr188) by MAPK/ERK. However, the acquisition of DNA binding and transactivation capacity of C/EBPβ is delayed until further phosphorylation (on Ser184 or Thr179) by GSK3β occurs. Phosphorylation by glycogen synthase kinase-3β (GSK3β) induces S phase entry and thereby mitotic clonal expansion (MCE), a requirement for terminal differentiation. Because MAPK activity is down-regulated before S phase is completed, we sought to identify the kinase that maintains C/EBPβ in the primed phosphorylated state throughout S phase and MCE. We show here that cdk2/cyclinA, whose expression is activated at the onset of S phase, functions in this capacity. Ex vivo and in vitro experiments show that cdk2/cyclinA catalyzes this delayed priming phosphorylation. Mass spectrometric analysis revealed that cdk2/cyclinA phosphorylates C/EBPβ on Thr188 and is required for phosphorylation (on Ser184 or Thr179) of C/EBPβ by GSK3β and maintenance of DNA binding activity. Suppression of cdk2 activity by RNA interference or pharmacologic inhibitor disrupts subsequent events in the differentiation program. Thus, MAPK and cdk2/cyclinA act sequentially to maintain Thr188 of C/EBPβ in the primed phosphorylated state during MCE and thereby progression of terminal differentiation. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 11597~11602 | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Role of cdk2 in the sequential phosphorylation/activation of C/EBPβ during adipocyte differentiation | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry & Molecular Biology (생화학,분자생물학) | - |
dc.contributor.googleauthor | Xi Li | - |
dc.contributor.googleauthor | Jae Woo Kim | - |
dc.contributor.googleauthor | Qi-Qun Tang | - |
dc.contributor.googleauthor | M. Daniel Lane | - |
dc.contributor.googleauthor | Henning Urlaub | - |
dc.contributor.googleauthor | Mads Grønborg | - |
dc.identifier.doi | 10.1073/pnas.0703771104 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00865 | - |
dc.relation.journalcode | J02550 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.contributor.alternativeName | Kim, Jae Woo | - |
dc.contributor.affiliatedAuthor | Kim, Jae Woo | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 104 | - |
dc.citation.number | 28 | - |
dc.citation.startPage | 11597 | - |
dc.citation.endPage | 11602 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.104(28) : 11597-11602, 2007 | - |
dc.identifier.rimsid | 50436 | - |
dc.type.rims | ART | - |
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