The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
p53 Down-Regulates CHK1 through p21 and the Retinoblastoma Protein
Open accessAbstract
Both fission yeast and mammalian cells require the function of the checkpoint kinase CHK1 for G2 arrest after DNA damage. The tumor suppressor p53, a well-studied stress response factor, has also been shown to play a role in DNA damage G2 arrest, although in a manner that is probably independent of CHK1. p53, however, can be phosphorylated and regulated by both CHK1 as well as another checkpoint kinase, hCds1 (also called CHK2). It was therefore of interest to determine whether reciprocally, p53 affects either CHK1 or CHK2. We found that induction of p53 either by diverse stress signals or ectopically using a tetracycline-regulated promoter causes a marked reduction in CHK1 protein levels. CHK1 downregulation by p53 occurs as a result of reduced CHK1 RNA accumulation, indicating that repression occurs at the level of transcription. Repression of CHK1 by p53 requires p21, since p21 alone is sufficient for this to occur and cells lacking p21 cannot downregulate CHK1. Interestingly, pRB is also required for CHK1 downregulation, suggesting the possible involvement of E2F-dependent transcription in the regulation of CHK1. Our results identify a new repression target of p53 and suggest that p53 and CHK1 play interdependent and complementary roles in regulating both the arrest and resumption of G2 after DNA damage.
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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
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113
DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
Shieh, S.-Y., Ikeda, M., Taya, Y., & Prives, C. (1997) · Cell · doi:10.1016/s0092-8674(00)80416-x · Cited by 2,100
Self-citationSanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997) · Science · doi:10.1126/science.277.5331.1497 · Cited by 1,320
Radiation-induced cell cycle arrest compromised by p21 deficiency
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“While G1 arrest relies extensively on the synthesis of p21 which is induced by p53 (11, 12, 24, 69, 70), it has been postulated that p53-mediated G2 arrest involves not only induction of p21 but other p53 targets such as 14-3-3-s (17, 32) and GADD45 (38).”
BackgroundShieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., & Prives, C. (2000) · Genes & Development · doi:10.1101/gad.14.3.289 · Cited by 972
Self-citation14-3-3σ is required to prevent mitotic catastrophe after DNA damage
Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Nature · doi:10.1038/44188 · Cited by 895
Agarwal, M. L., Agarwal, A., Taylor, W. R., & Stark, G. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8493 · Cited by 858
Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53
Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000) · Genes & Development · doi:10.1101/gad.14.3.278 · Cited by 805
Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21
Waldman, T., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1996) · Nature · doi:10.1038/381713a0 · Cited by 728
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
E2F integrates cell cycle progression with DNA repair, replication, and G 2 /M checkpoints
Ren, B., Cam, H., Takahashi, Y., Volkert, T., Terragni, J., Young, R. A., & Dynlacht, B. D. (2002) · Genes & Development · doi:10.1101/gad.949802 · Cited by 1,125
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971
Roles of Chk1 in cell biology and cancer therapy
Zhang, Y., & Hunter, T. (2014) · International Journal of Cancer · doi:10.1002/ijc.28226 · Cited by 462
Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time
Lukas, J., Lukas, C., & Bartek, J. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.03.006 · Cited by 381
Metadata
- Authors
- Gottifredi, V., Karni-Schmidt, O., Shieh, S.-Y., & Prives, C.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-02-01
- Volume
- 21
- Issue
- 4
- Pages
- 1066-1076
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2130200459
- Cited by
- 172
- References
- 12
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
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- Gottifredi, V., Karni-Schmidt, O., Shieh, S.-Y., & Prives, C. (2001). p53 Down-Regulates CHK1 through p21 and the Retinoblastoma Protein. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.21.4.1066-1076.2001
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