p53 suppresses the c-myb-induced activation of heat shock transcription factor 3

Expression of heat shock proteins (HSPs) is controlled by heat shock transc ription factors (HSFs), Vertebrates express multiple HSFs whose activities may be regulated by distinct signals. HSF3 is specifically activated in uns tressed proliferating cells by direct binding to the c-myb proto-oncogene p roduct (c-Myb), which plays an important role in cellular proliferation. Th is suggests that the c-Myb-induced HSF3 activation may contribute to the gr owth-regulated expression of HSPs, Here we report that the p53 tumor suppre ssor protein directly binds to HSF3 and blocks the interaction between c-My b and HSF3. In addition, p53 stimulates the degradation of c-Myb through a proteasome-dependent mechanism, which is, at least partly, mediated by indu ction of Siah in certain types of cells. Induction of p53 by a genotoxic re agent in DT40 cells disrupts the HSF3-c-Myb interaction and down-regulates the expression of certain HSPs, Mutated forms of p53 found in certain tumor s did not inhibit c-Myb-induced HSF3 activation. The regulation of HSF3 act ivity by c-Myb and p53 sheds light on the molecular events that govern HSP expression during cellular proliferation and apoptosis.