ArticleMolecular and cellular biology2010
The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells.BMC cancer · 2022Article
- CRL4Genes · 2022Review
- Regulation of DNA Replication Licensing and Re-Replication by Cdt1.International journal of molecular sciences · 2021Review
- DDB2 regulates DNA replication through PCNA-independent degradation of CDT2.Cell & bioscience · 2021Article
- TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51Cell reports · 2020Article
- Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases.Experimental & molecular medicine · 2020Review
- CRL4Cdt2 ubiquitin ligase regulates Dna2 and Rad16 (XPF) nucleases by targeting Pxd1 for degradation.PLoS genetics · 2020Article
- Review
- A single-parasite transcriptional atlas ofeLife · 2020Article
- Proliferating cell nuclear antigen interacts with the CRL4 ubiquitin ligase subunit CDT2 in DNA synthesis-induced degradation of CDT1.The Journal of biological chemistry · 2018Article
- Direct binding of Cdt2 to PCNA is important for targeting the CRL4Life science alliance · 2018Article
- Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork.Molecular cell · 2017Review
- Expression of an S phase-stabilized version of the CDK inhibitor Dacapo can alter endoreplication.Development (Cambridge, England) · 2015Article
- CRL4Cdt2 E3 ubiquitin ligase and proliferating cell nuclear antigen (PCNA) cooperate to degrade thymine DNA glycosylase in S phase.The Journal of biological chemistry · 2014Article
- Thymine DNA glycosylase is a CRL4Cdt2 substrate.The Journal of biological chemistry · 2014Article
- Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes.Nature · 2013Article
- Proteolysis of Xenopus Cip-type CDK inhibitor, p16Xic2, is regulated by PCNA binding and CDK2 phosphorylation.Cell division · 2013Article
- Epidermal growth factor receptor protects proliferating cell nuclear antigen from cullin 4A protein-mediated proteolysis.The Journal of biological chemistry · 2012Article
- Two different replication factor C proteins, Ctf18 and RFC1, separately control PCNA-CRL4Cdt2-mediated Cdt1 proteolysis during S phase and following UV irradiation.Molecular and cellular biology · 2012Article
- Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it is ubiquitinated and degraded. In this study, we show that the predominant E3 for Xic1 in the egg is the Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4(Cdt2)) ubiquitin ligase. The addition of full-length XCdt2 to the Xenopus extract promotes Xic1 turnover, while the N-terminal domain of XCdt2 (residues 1 to 400) cannot promote Xic1 turnover, despite its ability to bind both Xic1 and DDB1. Further analysis demonstrated that XCdt2 binds directly to PCNA through its C-terminal domain (residues 401 to 710), indicating that this interaction is important for promoting Xic1 turnover. We also identify the cis-acting sequences required for Xic1 binding to Cdt2. Xic1 binds to Cdt2 through two domains (residues 161 to 170 and 179 to 190) directly flanking the Xic1 PCNA binding domain (PIP box) but does not require PIP box sequences (residues 171 to 178). Similarly, human p21 binds to human Cdt2 through residues 156 to 161, adjacent to the p21 PIP box. In addition, we identify five lysine residues (K180, K182, K183, K188, and K193) immediately downstream of the Xic1 PIP box and within the second Cdt2 binding domain as critical sites for Xic1 ubiquitination. Our studies suggest a model in which both the CRL4(Cdt2) E3- and PIP box-containing substrates, like Xic1, are recruited to chromatin through independent direct associations with PCNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.