HSF4, A NEW MEMBER OF THE HUMAN HEAT-SHOCK FACTOR FAMILY WHICH LACKS PROPERTIES OF A TRANSCRIPTIONAL ACTIVATOR

Heat shock transcription factors (HSFs) mediate the inducible transcri ptional response of genes that encode heat shock proteins and molecula r chaperones. In vertebrates, three related HSF genes (HSF1 to -3) and the respective gene products (HSFs) have been characterized. We repor t the cloning and characterization of human HSF4 (hHSF4), a novel memb er of the hHSF family that shares properties with other members of the HSF family yet appears to be functionally distinct. hHSF4 lacks the c arboxyl-terminal hydrophobic repeat which is shared among all vertebra te HSFs and has been suggested to be involved in the negative regulati on of DNA binding activity. hHSF4 is preferentially expressed in the h uman heart, brain, skeletal muscle, and pancreas. Transient transfecti on of hHSF4 in HeLa cells, which do not express hHSF4, results in a co nstitutively active DNA binding trimer which, unlike other members of the HSF family, lacks the properties of a transcriptional activator. C onstitutive overexpression of hHSF4 in HeLa cells results in reduced e xpression of the endogenous hsp70, hsp90, and hsp27 genes. hHSF4 repre sents a novel hHSF that exhibits tissue-specific expression and functi ons to repress the expression of genes encoding heat shock proteins an d molecular chaperones.