The Transcriptional Program following p53 Activation
- R. ZHAO,
- K. GISH,
- M. MURPHY,
- Y. YIN,
- D. NOTTERMAN,
- W.H. HOFFMAN,
- E. TOM,
- D.H. MACK, and
- A.J. LEVINE
- *Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; †Genomics Research, Eos Biotechnology, South San Francisco, California 94080; ‡Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; §Department of Radiation Oncology, Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, New York 10032; ¶The Rockefeller University, New York, New York 10021
This extract was created in the absence of an abstract.
Excerpt
Slightly more than half of all human cancers sustainmutations in the p53 gene (Hollstein et al. 1991; Bennettet al. 1992), and germ-line mutations in this gene lead tovarious types of cancers (Malkin et al. 1990). The wildtype p53 gene can block cellular transformation by activated oncogenes in vitro (Finlay et al. 1989) and tumorcell growth in vivo (Shaw et al. 1992; Xu et al. 1997). Anormal cell maintains low levels of the p53 protein. Thelevels and the transcriptional activity of the p53 proteinincrease in response to cellular stress, such as DNA damage, activation of oncogenes, viral infection, hypoxia, orlow levels of ribonucleoside triphosphate pools (Levine1997). In response to increased levels of the p53 protein,cells undergo either cell cycle arrest or apoptosis depending on the level of p53, the cell type, or the presence orabsence of activated oncogenes. This eliminates affectedcells and prevents a high mutation rate by blocking theduplication of damaged DNA (Levine 1997; Prives andHall 1999)...
