Constitutive phosphorylation at Ser307 was shown to inhibit HSF1 transcriptional activity under normal temperatures. Substitution of Ser307 with alanine derepresses the transactivation domain such that the S307A mutant showed increased transcriptional activity in human and mouse cells (Knauf U et al. 1996; Kline MP & Morimoto RI 1997).
HSF1-ERK association was shown to promote ERK activity in human HeLa, acute monocytic leukemia THP1 and metastatic cutaneous SCC7 cells resulting in phosphorylation of HSF1 on Ser307 (Chu B et al. 1996; Wang X et al. 2004). This phosphorylation in turn promoted HSF1 association with YWHAE (14-3-3 epsilon), which may be involved in the attenuation of HSF1 activity during recovery and leads to accelerated cytoplasmic localization of HSF1 (Wang X et al. 2003, 2004).