TUMOR-SUPPRESSOR P53 GENE FORMS MULTIPLE ISOFORMS - EVIDENCE FOR SINGLE-LOCUS ORIGIN AND CYTOPLASMIC COMPLEX-FORMATION WITH HEAT-SHOCK PROTEINS

The tumor suppressor protein p53 is a major cell cycle control factor, and mutations in p53 are the most common genetic lesion found in huma n tumors, resulting in loss of function and contributing to malignant transformation. This report reviews several studies which show that p5 3 protein appears as at least eleven isoforms having the same amino ac id backbone but varying in charge by level of phosphorylation. All iso forms are derived from a single locus, which indicates that p53 activi ty is modulated by post-translational modification. In addition, mutan t p53 forms hetero-oligomers with two families of proteins: HSP70 and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed to protect p53 from proteolysis and are probably involved in t ranslocation of activated p53 from the cytoplasm to the nucleus for tr ansactivation of other cell cycle control genes.