HSF1 and cancer: GSK3 can phosphorylate HSF1 to inhibit its transcriptional activity by forcing its nuclear exclusion, thereby reducing expression of HSPs [38, 39]. This negative regulation of HSF1 implicates a novel role of GSK3 in proteostasis regulation and in some cancers reduced GSK3 activity may contribute to malignant transformation at least partially via HSF1 activation.