Functional HSF1 Requires Aromatic-Participant Interactions in Protecting Mouse Embryonic Fibroblasts against Apoptosis Via G2 Cell Cycle Arrest

Abstract

The present study highlighted the aromatic-participant interactions in in vivo trimerization of HSF1 and got an insight into the process of HSF1 protecting against apoptosis. In mouse embryonic fibroblasts (MEFs), mutations of mouse HSF1 (W37A, Y60A and F104A) resulted in a loss of trimerization activity, impaired binding of the heat shock element (HSE) and lack of heat shock protein 70 (HSP70) expression after a heat shock. Under UV irradiation, wildtype mouse HSF1 protected the MEFs from UV-induced apoptosis, but none of the mutants offered protection. We found that normal expression of HSF1 was essential to the cell arrest in G2 phase, assisting with the cell cycle checkpoint. The cells that lack normal HSF1 failed to arrest in the G2 phase, resulting in the process of cell apoptosis. We conclude that the treatment with UV or heat shock stresses appears to induce the approach of HSF1 monomers directly via aromatic-participant interactions, followed by the formation of a HSF1 trimer. HSF1 protects the MEFs from the stresses through the expression of HSPs and a G2 cell cycle arrest.

HSF1 Relieves Amyloid-β-Induced Cardiomyocytes Apoptosis

“…Our results showed that HSF1 also reversed the expression of HSPs, while it relieved apoptosis and ER stress induced by amyloid-b. HSPs are needed by HSF1 in protecting against apoptosis [31]. Overexpressing of HSP27 reduces amyloid-b-mediated cell death and protects against amyloid-b-induced damage [32].…”

“…Amyloid-b (Ab [25][26][27][28][29][30][31][32][33][34][35] ) was purchased from Bioss (Beijing, China) and dissolved in sterile water at the concentration of 0.94 mM. This stock solution was stored at -20°C but was kept at 37°C for 72 h before use.…”

Quantitative Analyses of Postmortem Heat Shock Protein mRNA Profiles in the Occipital Lobes of Human Cerebral Cortices: Implications in Cause of Death

“…Since HSPA7 and A13 are also known as inducible members of HSPs (Leung et al, 1992;Otterson et al, 1994), it can be postulated that these HSPs are not induced in subjects with ASP or acute heart failure as robustly as in those with TI. Rapid gene tran-A B scription of inducible HSP mRNAs primarily lies under the control of HSF1, acting on downstream target genes bearing heat shock elements in their promoter region (Chang et al, 2012;Fujimoto and Nakai, 2010), other cis-elements in the promoters often contribute to differential modes of transcriptional induction in different cellular contexts as well as by exposure to different types and severities of stressful stimuli (Diller, 2006;Stetler et al, 2010). Therefore, it is reasonable that circumstances of death can differentially influence transcriptional induction of each member of the inducible HSPs, leading to alterations in postmortem mRNA profiles.…”

The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence

“…In fact, elevated HSP expression has been identified in upper epidermal cells and HSP70 was shown to protect against ROS- or UVB-induced cell death in keratinocytes [131,132]. Following this line, mutated heat shock factor (HSF1) incapable of conveying HSP70 transactivation failed to prevent UV-induced apoptosis in mouse embryonic fibroblasts [133]. Thus, HSP70 seems to represent another pro-survival factor in irradiated potentially cancerous skin cells.…”