Heat Shock Transcription Factor 2 Is Significantly Involved in Neurodegenerative Diseases, Inflammatory Bowel Disease, Cancer, Male Infertility, and Fetal Alcohol Spectrum Disorder: The Novel Mechanisms of Several Severe Diseases.

HSF (heat shock transcription factor or heat shock factor) was discovered as a transcription factor indispensable for heat shock response. Although four classical HSFs were discovered in mammals and two major HSFs, HSF1 and HSF2, were cloned in the same year of 1991, only HSF1 was intensively studied because HSF1 can give rise to heat shock response through the induction of various HSPs' expression. On the other hand, HSF2 was not well studied for some time, which was probably due to an underestimate of HSF2 itself. Since the beginning of the 21st century, HSF2 research has progressed and many biologically significant functions of HSF2 have been revealed. For example, the roles of HSF2 in nervous system protection, inflammation, maintenance of mitosis and meiosis, and cancer cell survival and death have been gradually unveiled. However, we feel that the fact HSF2 has a relationship with various factors is not yet widely recognized; therefore, the biological significance of HSF2 has been underestimated. We strongly hope to widely communicate the significance of HSF2 to researchers and readers in broad research fields through this review. In addition, we also hope that many readers will have great interest in the molecular mechanism in which HSF2 acts as an active transcription factor and gene bookmarking mechanism of HSF2 during cell cycle progression, as is summarized in this review.