p21-induced cycle arrest in G1 protects cells from apoptosis induced by UV-irradiation or RNA polymerase II blockage
| Autor: | N Bissonnette, D J Hunting |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research Periodicity Cell cycle checkpoint Skin Neoplasms DNA damage Ultraviolet Rays RNA polymerase II Apoptosis Culture Media Serum-Free Cyclins Sequence-specific DNA binding Genetics Tumor Cells Cultured Mimosine Molecular Biology Polymerase biology Caspase 3 Carcinoma G1 Phase Cell cycle Cyclin-Dependent Kinases Cell biology Cysteine Endopeptidases Biochemistry Caspases Mutation biology.protein DNA fragmentation RNA Polymerase II Poly(ADP-ribose) Polymerases Tumor Suppressor Protein p53 DNA Damage |
| Zdroj: | Oncogene. 16(26) |
| ISSN: | 0950-9232 |
| Popis: | Cells expressing the R273H mutant of p53, which lacks sequence specific DNA binding capacity, do not undergo cell cycle arrest in G1 following exposure to ionizing or UV radiation because of their inability to induce p21Waf1/Cip1, a cyclin-dependent kinase inhibitor and downstream mediator of p53-dependent DNA damage-induced growth arrest. Following UV-irradiation or treatment with an inhibitor of RNA pol II, we observed a rapid induction of the apoptotic process, as evidenced by DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase. Using mimosine, a p21Waf1/Cip1 inducer that bypasses the requirement for transcriptional transactivation by p53, we demonstrated that a G1 cell cycle arrest can prevent apoptosis following UV-irradiation or treatment with an RNA polymerase II inhibitor. Serum starvation, which also synchronized cells in G1 but did not induce p21Waf1/Cip1, did not protect cells from apoptosis. These results demonstrate that restoring a late G1 checkpoint by inducing p21Waf1/Cip1 expression can protect cells from DNA damage induced apoptosis. Our results suggest that p21Waf1/Cip1 can interrupt the apoptotic process at a point downstream from p53 accumulation but upstream from caspase-3 activation. |
| Databáze: | OpenAIRE |
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