A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1 - PubMed (original) (raw)
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1
Jianping Jin et al. Mol Cell. 2006.
Free article
Abstract
Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta propeller Ddb1 adaptor protein, but few substrate receptors have been identified. Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. DCAF2/Cdt2, which is related to S. pombe Cdt2, functions in Xenopus egg extracts and human cells to destroy the replication licensing protein Cdt1 in S phase and after DNA damage. Depletion of human Cdt2 causes rereplication and checkpoint activation. In Xenopus, Cdt2 is recruited to replication forks via Cdt1 and PCNA, where Cdt1 ubiquitylation occurs. These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication.
Similar articles
- L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage.
Higa LA, Banks D, Wu M, Kobayashi R, Sun H, Zhang H. Higa LA, et al. Cell Cycle. 2006 Aug;5(15):1675-80. doi: 10.4161/cc.5.15.3149. Epub 2006 Aug 1. Cell Cycle. 2006. PMID: 16861906 - DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.
Sansam CL, Shepard JL, Lai K, Ianari A, Danielian PS, Amsterdam A, Hopkins N, Lees JA. Sansam CL, et al. Genes Dev. 2006 Nov 15;20(22):3117-29. doi: 10.1101/gad.1482106. Epub 2006 Nov 3. Genes Dev. 2006. PMID: 17085480 Free PMC article. - CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation.
Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H. Higa LA, et al. Nat Cell Biol. 2006 Nov;8(11):1277-83. doi: 10.1038/ncb1490. Epub 2006 Oct 15. Nat Cell Biol. 2006. PMID: 17041588 - Ubiquitin proteasome system (UPS): what can chromatin do for you?
O'Connell BC, Harper JW. O'Connell BC, et al. Curr Opin Cell Biol. 2007 Apr;19(2):206-14. doi: 10.1016/j.ceb.2007.02.014. Epub 2007 Feb 20. Curr Opin Cell Biol. 2007. PMID: 17314036 Review. - Regulation of DNA Replication Licensing and Re-Replication by Cdt1.
Zhang H. Zhang H. Int J Mol Sci. 2021 May 14;22(10):5195. doi: 10.3390/ijms22105195. Int J Mol Sci. 2021. PMID: 34068957 Free PMC article. Review.
Cited by
- The Multifunctions of WD40 Proteins in Genome Integrity and Cell Cycle Progression.
Zhang C, Zhang F. Zhang C, et al. J Genomics. 2015 Feb 5;3:40-50. doi: 10.7150/jgen.11015. eCollection 2015. J Genomics. 2015. PMID: 25653723 Free PMC article. Review. - Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease.
Lee J, Zhou P. Lee J, et al. Front Oncol. 2012 Mar 6;2:21. doi: 10.3389/fonc.2012.00021. eCollection 2012. Front Oncol. 2012. PMID: 22649780 Free PMC article. - Cullin-RING Ligases as attractive anti-cancer targets.
Zhao Y, Sun Y. Zhao Y, et al. Curr Pharm Des. 2013;19(18):3215-25. doi: 10.2174/13816128113199990300. Curr Pharm Des. 2013. PMID: 23151137 Free PMC article. Review. - The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.
Cheng J, Guo J, North BJ, Tao K, Zhou P, Wei W. Cheng J, et al. Biochim Biophys Acta Rev Cancer. 2019 Jan;1871(1):138-159. doi: 10.1016/j.bbcan.2018.11.007. Epub 2018 Dec 30. Biochim Biophys Acta Rev Cancer. 2019. PMID: 30602127 Free PMC article. Review. - Structural assembly of cullin-RING ubiquitin ligase complexes.
Zimmerman ES, Schulman BA, Zheng N. Zimmerman ES, et al. Curr Opin Struct Biol. 2010 Dec;20(6):714-21. doi: 10.1016/j.sbi.2010.08.010. Epub 2010 Sep 27. Curr Opin Struct Biol. 2010. PMID: 20880695 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous