Biochemical, immunological, and functional aspects of the growth-suppressor/oncoprotein p53.

The cellular phosphoprotein p53 was initially discovered in a variety of in vitro transformed and tumor-derived cell lines. Later on, p53 was also found in normal, nontransformed cells albeit at very low levels. Inhibition of p53 functions by microinjection of anti-p53 antibodies prevented quiescent cells from reentering the cell cycle after serum stimulation, indicating that p53 might somehow be involved in the regulation of cell proliferation. After detection of p53-specific mRNAs, the gene was discovered in diverse species ranging from fish and frog to man. Knowing the p53 DNA sequence, it became clear that mutant forms of p53 had immortalizing and, in cooperation with other oncogenes, transforming activities. On the other hand, wild-type p53 could suppress oncogene-mediated transformation. It seems clear now that wild-type p53 is a tumor suppressor. Moreover, analysis of p53 from many types of human tumors indicates that the p53 gene is a very frequent target for mutational alterations. Because the biochemical consequences of these alterations are not yet clear, it is not understood yet on the molecular level how p53 can act as an oncogenic protein, on one hand, and as a growth-suppressor protein on the other hand. Therefore, the present review aims to summarize the biochemical and immunological properties of p53 and to address some biological activities of p53 in order to allow more insight into how p53 might be regulated within the cell or how p53 might regulate cell proliferation.