HSF1 and cancer: In contrast to the elevated HSF1 degradation in HD, compromised FBXW7 function in cancers impairs HSF1 degradation, giving rise to increased HSF1 protein levels that support malignancy (45, 46, 47, 48).These and other studies demonstrate the importance of protein-protein interactions in modulating HSF1 nuclear retention, DNA binding, activation or repression of target genes, and degradation (8, 10, 22, 49, 50, 51, 52).