Oligomerization of oncoprotein p53.
Cellular phosphoprotein p53, which seems to be a multifunctional protein, may be assigned to different structural subclasses. Recently established immortalized or transformed cell lines that overexpress p53 allowed us to perform a detailed analysis of the quaternary structure of p53. By means of sucrose density gradient centrifugation, we found in simian virus 40-transformed cells that overexpress p53, in addition to high-molecular-weight T-p53 complexes, low-molecular-weight forms. The level of T-p53 complexes within simian virus 40-transformed cells seemed to be determined by the intracellular concentration of p53. However, the presence of uncomplexed T antigen and p53 indicated that an appropriate modification of at least one of the two proteins appears to be necessary for complex formation. Using different monoclonal antibodies that distinguish between (i) p53 associated with T antigen or heat shock proteins and (ii) p53 in apparently free form, we found p53 from transformed cells always in high-molecular-weight forms. p53 from normal and immortalized cells, however, was found mainly in low-molecular-weight forms. Pulse-labeling experiments revealed that oligomerization of p53 is a very rapid process. Monomeric forms of p53 which could be detected only by 2 min of pulse-labeling were rapidly converted to stable, high-molecular-weight oligomers. Furthermore, our data indicate a correlation between the occurrence of p53 in high-molecular-weight forms and the transformation state of the cell.
D000818:Animals; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002499:Centrifugation, Density Gradient; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011108:Polymers; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D016159:Tumor Suppressor Protein p53
D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011108:Polymers; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53