Regulation of HSF1 protein stabilization: An updated review

Heat shock factor 1 (HSF1) is a transcriptional factor that determines the efficiency of heat shock responses (HSRs) in the cell. Given its function has been extensively studied in recent years, HSF1 is considered a potential target for the treatment of disorders associated with protein aggregation. The activity of HSF1 is traditionally regulated at the transcriptional level in which the transactivation domain of HSF1 is modified by extensive array of pos-translational modifications, such as phosphorylation, sumoylation, and acetylation. Recently, HSF1 is also reported to be regulated at the monomeric level. For example, in neurodegenerative disorders such as Huntington's disease and Alzheimer's disease the expression levels of the monomeric HSF1 are found to be reduced markedly. Methylene blue (MB) and riluzole, two clinical available drugs, increase the amount of the monomeric HSF1 in both cells and animals. Since the monomeric HSF1 not only determines the efficiency of HSRs, but exerts protective effects in a trimerization-independent manner, increasing the amount of the monomeric HSF1 via stabilization of HSF1 may be an alternative strategy for the amplification of HSR. However, to date we have no outlined knowledges about HSF1 protein stabilization, though studies regarding the regulation of the monomeric HSF1 have been documented in recent years. Here, we summarize the regulation of the monomeric HSF1 by some previously reported factors, such as synuclein, Huntingtin (Htt), TDP-43, unfolded protein response (UPR), MB and doxorubicin (DOX), as well as their possible mechanisms, aiming to push the understanding about HSF1 protein stabilization.