2008年9月15日
PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex.
Genes & development
- ,
- ,
- ,
- ,
- ,
- 巻
- 22
- 号
- 18
- 開始ページ
- 2496
- 終了ページ
- 506
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1101/gad.1676108
- 出版者・発行元
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
The DNA polymerase delta processivity factor Proliferating Cell Nuclear Antigen (PCNA) promotes the DNA damage-induced degradation of the replication initiation factor Cdt1 via the CRL4(Cdt2) E3 ubiquitin ligase complex. Here we demonstrate that PCNA promotes the ubiquitylation and degradation of the CDK inhibitor p21 in cells irradiated with low dose of ultraviolet (UV) by a similar mechanism. Human cells that are depleted of Cul4, DDB1 (damage-specific DNA-binding protein-1), or the DCAF Cdt2, are deficient in the UV-induced ubiquitylation and degradation of p21. Depletion of mammalian cells of PCNA by siRNA, or mutations in p21 that abrogate PCNA binding, prevent UV-induced p21 ubiquitylation and degradation, indicating that physical binding with PCNA is necessary for the efficient ubiquitylation of p21 via the CRL4(Cdt2) ubiquitin ligase. Cdt2 functions as the substrate recruiting factor for p21 to the rest of the CRL4 ubiquitin ligase complex. The CRL4(Cdt2) E3 ubiquitin ligase ubiquitylates p21 both in vivo and in vitro, and its activity is dependent on the interaction of p21 with PCNA. Finally, we show that the CRL4(Cdt2) and the SCF(Skp2) ubiquitin ligases are redundant with each other in promoting the degradation of p21 during an unperturbed S phase of the cell cycle.
- リンク情報
-
- DOI
- https://doi.org/10.1101/gad.1676108
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/18794347
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546691
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000259221000006&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=51949098691&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=51949098691&origin=inward
- ID情報
-
- DOI : 10.1101/gad.1676108
- ISSN : 0890-9369
- eISSN : 1549-5477
- PubMed ID : 18794347
- PubMed Central 記事ID : PMC2546691
- SCOPUS ID : 51949098691
- Web of Science ID : WOS:000259221000006