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Article

CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.

The Journal of biological chemistry - 24 Oct 2008

Nishitani Hideo, Shiomi Yasushi, Iida Hiroka, Michishita Masato, Takami Toshihiro, Tsurimoto Toshiki

Abstract excerpt

Previous reports showed that chromatin-associated PCNA couples DNA replication with Cul4-DDB1(Cdt2)-dependent proteolysis of the licensing factor Cdt1. The CDK inhibitor p21, another PCNA-binding protein, is also degraded both in S phase and after UV irradiation. Here we show that p21 is degraded by the same ubiquitin-proteasome pathway as Cdt1 in HeLa cells. When PCNA or components of Cul4-DDB1(Cdt2) were...

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Source

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Identifiers

PMID: 18703516
DOI: 10.1074/jbc.M806045200
PMCID: PMC2662008

Genes

DDB1
PCNA

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

Related research

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Research trail→

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CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.PMID 18703516Read ↗

An Evolutionarily Conserved Function of Proliferating Cell Nuclear Antigen for Cdt1 Degradation by the Cul4-Ddb1 Ubiquitin Ligase in Response to DNA DamageSemantic proximity Read ↗

CRL4Cdt2 E3 ubiquitin ligase and proliferating cell nuclear antigen (PCNA) cooperate to degrade thymine DNA glycosylase in S phase.Semantic proximity Read ↗

DDB2 association with PCNA is required for its degradation after UV-induced DNA damage.Semantic proximity Read ↗

Degradation of p21CDKN1A after DNA damage is independent of type of lesion, and is not required for DNA repair.Semantic proximity Read ↗

Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation.Semantic proximity Read ↗

CDKs Promote DNA Replication Origin Licensing in Human Cells by Protecting Cdc6 from APC/C-Dependent ProteolysisSemantic proximity Read ↗

Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication.Semantic proximity Read ↗

p21 contains independent binding sites for cyclin and cdk2: both sites are required to inhibit cdk2 kinase activity.Semantic proximity Read ↗

PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication StressSemantic proximity Read ↗

The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA.Semantic proximity Read ↗

CRL4<sup>Cdt2</sup>Semantic proximity Read ↗

Mutations at multiple CDK phosphorylation consensus sites on Cdt2 increase the affinity of CRL4Cdt2 for PCNA and its ubiquitination activity in S phase.Semantic proximity Read ↗

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