The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
CDK Inhibitor p21 Is Degraded by a Proliferating Cell Nuclear Antigen-coupled Cul4-DDB1Cdt2 Pathway during S Phase and after UV Irradiation
Open accessAbstract
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 silenced or when the PCNA binding site on p21 was mutated, degradation of p21 was prevented both in S phase and after UV irradiation. p21 was co-immunoprecipitated with Cul4A and DDB1 proteins when expressed in cells. The purified Cul4A-DDB1(Cdt2) complex ubiquitinated p21 in vitro. Consistently, p21 protein levels are low during S phase and increase around G(2) phase. Mutational analysis suggested that in addition to the PCNA binding domain, its flanking regions are also important for recognition by Cul4-DDB1(Cdt2). Our findings provide a new aspect of proteolytic control of p21 during the cell cycle.
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Cites
The SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114
Jin, J., Arias, E. E., Chen, J., Harper, J. W., & Walter, J. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.010 · Cited by 632
UV Irradiation Triggers Ubiquitin-Dependent Degradation of p21WAF1 to Promote DNA Repair
Bendjennat, M., Boulaire, J., Jascur, T., Brickner, H., Barbier, V., Sarasin, A., Fotedar, A., & Fotedar, R. (2003) · Cell · doi:10.1016/j.cell.2003.08.001 · Cited by 248
Cited by
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712
Multiple roles of the cell cycle inhibitor p21CDKN1A in the DNA damage response
Cazzalini, O., Scovassi, A. I., Savio, M., Stivala, L. A., & Prosperi, E. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.01.009 · Cited by 433
Examination of the expanding pathways for the regulation of p21 expression and activity
Jung, Y.-S., Qian, Y., & Chen, X. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.01.013 · Cited by 423
CRL4s: the CUL4-RING E3 ubiquitin ligases
Jackson, S., & Xiong, Y. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.07.002 · Cited by 411
Barr, A. R., Cooper, S., Heldt, F. S., Butera, F., Stoy, H., Mansfeld, J., Novák, B., & Bakal, C. (2017) · Nature Communications · doi:10.1038/ncomms14728 · Cited by 403
Metadata
- Authors
- Nishitani, H., Shiomi, Y., Iida, H., Michishita, M., Takami, T., & Tsurimoto, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 283
- Issue
- 43
- Pages
- 29045-29052
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1989149017
- Cited by
- 240
- References
- 3
- FWCI
- 8.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Nishitani, H., Shiomi, Y., Iida, H., Michishita, M., Takami, T., & Tsurimoto, T. (2008). CDK Inhibitor p21 Is Degraded by a Proliferating Cell Nuclear Antigen-coupled Cul4-DDB1Cdt2 Pathway during S Phase and after UV Irradiation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m806045200
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