Rapid Destruction of Human Cdc25A in Response to DNA Damage
作者： Niels Mailand , Jacob Falck , Claudia Lukas , Randi G Syljuåsen , Markus Welcker
DOI: 10.1126/SCIENCE.288.5470.1425
关键词:
摘要: To protect genome integrity and ensure survival, eukaryotic cells exposed to genotoxic stress cease proliferating provide time for DNA repair. Human responded ultraviolet light or ionizing radiation by rapid, ubiquitin- proteasome-dependent protein degradation of Cdc25A, a phosphatase that is required progression from G1 S phase the cell cycle. This response involved activated Chk1 kinase but not p53 pathway, persisting inhibitory tyrosine phosphorylation Cdk2 blocked entry into replication. Overexpression Cdc25A bypassed this mechanism, leading enhanced damage decreased survival. These results identify specific as part checkpoint mechanism suggest how overexpression in human cancers might contribute tumorigenesis.
sciencemag.org
harvard.edu参考文章(30)
I. Hoffmann, G. Draetta, E. Karsenti, Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. The EMBO Journal. ,vol. 13, pp. 4302- 4310 ,(1994) , 10.1002/J.1460-2075.1994.TB06750.X
Randy Yat Choi Poon, Man Sang Chau, Tony R. Hunter, Katsumi Yamashita, The Role of Cdc2 Feedback Loop Control in the DNA Damage Checkpoint in Mammalian Cells Cancer Research. ,vol. 57, pp. 5168- 5178 ,(1997)
T. Weinert, CELL CYCLE: Enhanced: A DNA Damage Checkpoint Meets the Cell Cycle Engine Science. ,vol. 277, pp. 1450- 1451 ,(1997) , 10.1126/SCIENCE.277.5331.1450
Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein, Genetic instabilities in human cancers Nature. ,vol. 396, pp. 643- 649 ,(1998) , 10.1038/25292
Garrett Walsh, Bonnie L. Kemp, Li Mao, You Hong Fan, Weiguo Wu, Overexpression of cdc25A and cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc Cancer Research. ,vol. 58, pp. 4082- 4085 ,(1998)
Beth Furnari, Nicholas Rhind, Paul Russell, Cdc25 Mitotic Inducer Targeted by Chk1 DNA Damage Checkpoint Kinase Science. ,vol. 277, pp. 1495- 1497 ,(1997) , 10.1126/SCIENCE.277.5331.1495
X Lu, Differential induction of transcriptionally active p53 following UV or ionizing radiation : defects in chromosome instability syndromes ? Cell. ,vol. 75, pp. 765- 778 ,(1993) , 10.1016/0092-8674(93)90496-D
Giulio Draetta, Jens Eckstein, Cdc25 protein phosphatases in cell proliferation Biochimica et Biophysica Acta. ,vol. 1332, ,(1997) , 10.1016/S0304-419X(96)00049-2
Arnold J Levine, p53, the Cellular Gatekeeper for Growth and Division Cell. ,vol. 88, pp. 323- 331 ,(1997) , 10.1016/S0092-8674(00)81871-1
Jiri LUKAS, Giulio DRAETTA, Jiri BARTEK, Distinct forms of human CDC2 identified by novel monoclonal antibodies. FEBS Journal. ,vol. 207, pp. 169- 176 ,(1992) , 10.1111/J.1432-1033.1992.TB17034.X