Havens CG and Walter JC (2009), Docking of a specialized PIP Box onto chromatin...

XB-ART-40031

Mol Cell 2009 Jul 10;351:93-104. doi: 10.1016/j.molcel.2009.05.012.

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Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2.

Havens CG , Walter JC .

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Substrates of the E3 ubiquitin ligase CRL4(Cdt2), including Cdt1 and p21, contain a PCNA-binding motif called a PIP box. Upon binding of the PIP box to PCNA on chromatin, CRL4(Cdt2) is recruited and the substrate is ubiquitylated. Importantly, a PIP box cannot be sufficient for destruction, as most PIP box proteins are stable. Using Xenopus egg extracts, we identify two sequence elements in CRL4(Cdt2) substrates that promote their proteolysis: a specialized PIP box that confers exceptionally efficient PCNA binding and a basic amino acid 4 residues downstream of the PIP box, which recruits CRL4(Cdt2) to the substrate-PCNA complex. We also identify two mechanisms that couple CRL4(Cdt2)-dependent proteolysis to the chromatin-bound form of PCNA, ensuring that this proteolysis pathway is active only in S phase or after DNA damage. Thus, CRL4(Cdt2) recognizes an unusual degron, which is assembled specifically on chromatin via the binding of a specialized PIP box to PCNA.

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Species referenced: Xenopus
Genes referenced: cdkn1a cdt1 pcna

References [+] :

Abbas, PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. 2008, Pubmed