Functional implications of the growth-suppressor oncoprotein p53

The nuclear phosphoprotein p53, named according to its apparent molecular weight on SDS-polyacrylamide gels is expressed, albeit at low levels, in a variety of cell types. In normal cells, it seems to be required for cell proliferation whereas in transformed cells it is frequently a target for mutations. Wild-type p53 has a growth-suppressor function which is completely abolished in mutant p53. However, there is ample evidence that mutant p53 has not only lost the suppressor activity but contributes as a dominant oncogene to tumorigenesis. In line with these observations wild-type p53 has a growth inhibitory function even when introduced in rapidly proliferating tumor cells whereas mutant p53 has a growth promoting function. Wild-type p53 and mutant p53 exhibit different DNA binding activities which may be implicated in transcriptional regulation and in DNA replication. Furthermore, both wild-type and mutant p53 play a role in controlling the transition of cells through at least two different restriction points of the cell cycle. Besides these functions in growth control p53 also plays an active role during embryonic development. Expression of p53 is high in cells predetermined to differentiate and decreases upon differentiation. Since embryonic cells express wild-type p53, a progressive role during differentiation has to be attributed to wild-type p53. Thus, this review will try to highlight some of the significant advances in the most rapidly evolving field of the functional implications of p53 in cell biology and tumorigenesis.