Proline 152 mutation in p53 abolishes cognate DNA binding, induces gain of function tumorigenesis

We have identified a relatively rare mutation in p53 in an Indian oral cancer patient sample at the fade end of its DNA binding domain [P152L]. Although P152L p53 DBD potentially binds to DNA, the full length protein is completely devoid of cognate site DNA binding ability. Also the mutant protein can efficiently tetramerize. Significantly, this mutant was found to induce cell mobility and proliferation with greater tumorigenic potential in nude mice, the mechanistic details of which is also investigated upon. These data establish P152L as a new gain of function p53 mutation Overall design: In order to gain the mechanistic insights of the gain-of-function effects elicited by P152L p53, RNA sequencing was performed for RNA from the tumor obtained (pCMV10 Ctrl and P152L p53) from xenograft experiment