The p53 tumor suppressor protein, a modulator of cell proliferation.
The p53 tumor suppressor protein, a modulator of cell proliferation.
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DOI：
10.1016/s0021-9258(19)49524-0
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发表时间：
1992-08
期刊：
影响因子：
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通讯作者：
S. Ullrich;Carl W. Anderson;W. Mercer;E. Appella
中科院分区：
文献类型：
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作者：
S. Ullrich;Carl W. Anderson;W. Mercer;E. Appella
From the $ Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, the $ Biology Department, Brookhaven National Laboratory, Upton, New York 11973, and the VDepartment of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 p53 was first described as a cellular protein which co-precipitated with the large T antigen of simian virus 40 (SV40) and whose synthesis was enhanced in chemically transformed tumors (1-3). Intense research has resulted in isolation of clones for homologous-p53 cDNAs and genes from diverse organisms (Fig. 1) and extensive characterization of the encoded nuclear phosphoprotein (reviewed in Ref. 4). Genetic evidence suggests that the p53 gene is a member of a family of tumor suppressor genes (5-7). p53 is the gene most frequently found to be mutated in a wide variety of human tumors (8). The molecular mechanisms of p53 function remain unknown; however, accumulating evidence suggests that p53 regulates expression of cell cycle-related genes (9, 10). p53 appears to have two conformations (11, 12); one is associated with the ability to block cell cycle progression and is unique to the wild type (wt)’protein; the second is associated with the ability to promote cell proliferation and may be common to mutant forms and wt-p53 alike. The ability to switch between two conformational states could explain apparently contradictory properties of p53 in normal cells. Recent reviews have focused on the structure of p53 and its role in cancer (4, 13-15). Here, we focus on the role of p53 in controlling cell proliferation, and we review recent data which show how post-translational modifications may regulate p53 conformation to produce both growthstimulating and growth-inhibiting effects.
