Opposing Effects of Ras on p53: Transcriptional Activation of mdm2 and Induction of p19ARF
作者： Stefan Ries , Carola Biederer , Douglas Woods , Ohad Shifman , Senji Shirasawa
DOI: 10.1016/S0092-8674(00)00123-9
关键词:
摘要: Mdm2 acts as a major regulator of the tumor suppressor p53 by targeting its destruction. Here, we show that mdm2 gene is also regulated Ras-driven Raf/MEK/MAP kinase pathway, in p53-independent manner. induced activated Raf degrades absence inhibitor p19ARF. This regulatory pathway accounts for observation cells transformed oncogenic Ras are more resistant to p53-dependent apoptosis following exposure DNA damage. Activation Ras-induced may therefore play key role suppressing during development and treatment. In primary cells, activates Levels determined opposing effects Raf-induced p19ARF Mdm2.
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sci-hub.se 参考文章(69)
Steven M. Picksley, David P. Lane, What the papers say: The p53-mdm2 autoregulatory feedback loop: A paradigm for the regulation of growth control by p53? BioEssays. ,vol. 15, pp. 689- 690 ,(1993) , 10.1002/BIES.950151008
Fred Bunz, A Dutriaux, C Lengauer, T Waldman, Shibin Zhou, JP Brown, JM Sedivy, Kenneth W Kinzler, Bert Vogelstein, Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage Science. ,vol. 282, pp. 1497- 1501 ,(1998) , 10.1126/SCIENCE.282.5393.1497
Ygal Haupt, Ruth Maya, Anat Kazaz, Moshe Oren, Mdm2 promotes the rapid degradation of p53 Nature. ,vol. 387, pp. 296- 299 ,(1997) , 10.1038/387296A0
Kathleen F. Pirollo, Yue Ao Tong, Zulema Villegas, Yawen Chen, Esther H. Chang, Oncogene-Transformed NIH 3T3 Cells Display Radiation Resistance Levels Indicative of a Signal Transduction Pathway Leading to the Radiation-Resistant Phenotype Radiation Research. ,vol. 135, pp. 234- 243 ,(1993) , 10.2307/3578300
J. D. Oliner, K. W. Kinzler, P. S. Meltzer, D. L. George, B. Vogelstein, Amplification of a gene encoding a p53-associated protein in human sarcomas Nature. ,vol. 358, pp. 80- 83 ,(1992) , 10.1038/358080A0
Kenneth W Kinzler, Bert Vogelstein, Lessons from Hereditary Colorectal Cancer Cell. ,vol. 87, pp. 159- 170 ,(1996) , 10.1016/S0092-8674(00)81333-1
Nancy C. Andrews, Douglas V. Faller, A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Research. ,vol. 19, pp. 2499- 2499 ,(1991) , 10.1093/NAR/19.9.2499
Jamil Momand, Gerard P. Zambetti, David C. Olson, Donna George, Arnold J. Levine, The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation Cell. ,vol. 69, pp. 1237- 1245 ,(1992) , 10.1016/0092-8674(92)90644-R
E. de Stanchina, M. E. McCurrach, F. Zindy, S.-Y. Shieh, G. Ferbeyre, A. V. Samuelson, C. Prives, M. F. Roussel, C. J. Sherr, S. W. Lowe, E1A signaling to p53 involves the p19(ARF) tumor suppressor. Genes & Development. ,vol. 12, pp. 2434- 2442 ,(1998) , 10.1101/GAD.12.15.2434
Y Barak, E Gottlieb, T Juven-Gershon, M Oren, Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes & Development. ,vol. 8, pp. 1739- 1749 ,(1994) , 10.1101/GAD.8.15.1739