Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Genes Dev. August 1, 2011; 25 (15): 1568-82.

Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase.

Havens CG , Walter JC .

Eukaryotic cell cycle transitions are driven by E3 ubiquitin ligases that catalyze the ubiquitylation and destruction of specific protein targets. For example, the anaphase-promoting complex/cyclosome (APC/C) promotes the exit from mitosis via destruction of securin and mitotic cyclins, whereas CRL1(Skp2) allows entry into S phase by targeting the destruction of the cyclin-dependent kinase (CDK) inhibitor p27. Recently, an E3 ubiquitin ligase called CRL4(Cdt2) has been characterized, which couples proteolysis to DNA synthesis via an unusual mechanism that involves display of substrate degrons on the DNA polymerase processivity factor PCNA. Through its destruction of Cdt1, p21, and Set8, CRL4(Cdt2) has emerged as a master regulator that prevents rereplication in S phase. In addition, it also targets other factors such as E2F and DNA polymerase η. In this review, we discuss our current understanding of the molecular mechanism of substrate recognition by CRL4(Cdt2) and how this E3 ligase helps to maintain genome integrity.

PubMed ID: 21828267
PMC ID: PMC3182024
Article link: Genes Dev.
Grant support: GM80676 NIGMS NIH HHS , R01 GM080676 NIGMS NIH HHS , GM80676 NIGMS NIH HHS

Genes referenced: cdkn1a cdt1 dtl pcna

Soucy, 2009, Pubmed[+]

My Xenbase: [ Log-in / Register ]
version: [4.3.1]

Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556