Different tumor-derived p53 mutants exhibit distinct biological activities.
In its wild-type form, the protein p53 can interfere with neoplastic processes. Tumor-derived cells often express mutant p53. Full-length mutant forms of p53 isolated so far from transformed mouse cells exhibit three common properties in vitro: loss of transformation-suppressing activity, gain of pronounced transforming potential, and ability to bind the heat shock protein cognate hsc70. A tumor-derived mouse p53 variant is now described, whose site of mutation corresponds to a hot spot for p53 in human tumors. While absolutely nonsuppressing, it is only weakly transforming and exhibits no detectable hsc70 binding. The data suggest that the ability of a p53 mutant to bind endogenous p53 is not the sole determinant of its oncogenic potential. The data also support the existence of gain-of-function p53 mutants.
Halevy
O
O
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Michalovitz
D
D
Oren
M
M
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53