The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex
Open accessAbstract
The DNA polymerase delta processivity factor Proliferating Cell Nuclear Antigen (PCNA) promotes the DNA damage-induced degradation of the replication initiation factor Cdt1 via the CRL4 Cdt2 E3 ubiquitin ligase complex. Here we demonstrate that PCNA promotes the ubiquitylation and degradation of the CDK inhibitor p21 in cells irradiated with low dose of ultraviolet (UV) by a similar mechanism. Human cells that are depleted of Cul4, DDB1 (damage-specific DNA-binding protein-1), or the DCAF Cdt2, are deficient in the UV-induced ubiquitylation and degradation of p21. Depletion of mammalian cells of PCNA by siRNA, or mutations in p21 that abrogate PCNA binding, prevent UV-induced p21 ubiquitylation and degradation, indicating that physical binding with PCNA is necessary for the efficient ubiquitylation of p21 via the CRL4 Cdt2 ubiquitin ligase. Cdt2 functions as the substrate recruiting factor for p21 to the rest of the CRL4 ubiquitin ligase complex. The CRL4 Cdt2 E3 ubiquitin ligase ubiquitylates p21 both in vivo and in vitro, and its activity is dependent on the interaction of p21 with PCNA. Finally, we show that the CRL4 Cdt2 and the SCF Skp2 ubiquitin ligases are redundant with each other in promoting the degradation of p21 during an unperturbed S phase of the cell cycle.
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Cites
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
Radiation-induced cell cycle arrest compromised by p21 deficiency
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“p21 inhibits the kinase activity of Cdk2, thereby preventing progression into or through the S phase of the cell cycle (Brugarolas et al. 1995).”
BackgroundMéndez, J., & Stillman, B. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8602-8612.2000 · Cited by 915
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Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase
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Self-citationTargeting of protein ubiquitination by BTB–Cullin 3–Roc1 ubiquitin ligases
Furukawa, M., He, Y. J., Borchers, C., & Xiong, Y. (2003) · Nature Cell Biology · doi:10.1038/ncb1056 · Cited by 458
Small RNAs with Imperfect Match to Endogenous mRNA Repress Translation
Saxena, S., Jónsson, Z. O., & Dutta, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307089200 · Cited by 436
Self-citationHuman CUL-1 associates with the SKP1/SKP2 complex and regulates p21 CIP1/WAF1 and cyclin D proteins
Yu, Z.-K., Gervais, J. L. M., & Zhang, H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11324 · Cited by 411
Two E3 ubiquitin ligases, SCF‐Skp2 and DDB1‐Cul4, target human Cdt1 for proteolysis
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Human De-Etiolated-1 Regulates c-Jun by Assembling a CUL4A Ubiquitin Ligase
Wertz, I. E., O'Rourke, K. M., Zhang, Z., Dornan, D., Arnott, D., Deshaies, R. J., & Dixit, V. M. (2004) · Science · doi:10.1126/science.1093549 · Cited by 365
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
Self-citationVan Roey, K., Uyar, B., Weatheritt, R. J., Dinkel, H., Seiler, M., Budd, A., Gibson, T. J., & Davey, N. E. (2014) · Chemical Reviews · doi:10.1021/cr400585q · Cited by 502
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
Metadata
- Authors
- Abbas, T., Sivaprasad, U., Terai, K., Amador, V., Pagano, M., & Dutta, A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-09-15
- Volume
- 22
- Issue
- 18
- Pages
- 2496-2506
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2113126688
- Cited by
- 366
- References
- 33
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Abbas, T., Sivaprasad, U., Terai, K., Amador, V., Pagano, M., & Dutta, A. (2008). PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes & Development. https://doi.org/10.1101/gad.1676108
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