Abstract
Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.
Highlights
Academic Editor: Jürg BählerReceived: 8 March 2021Accepted: 29 March 2021Published: 31 March 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Licensee MDPI, Basel, Switzerland.Cells are constantly being exposed to various forms of cellular stresses and external insults
This review focuses solely on heat shock factor 4 (HSF4), and we discuss the current understanding of the molecular properties and roles of HSF4 in health and diseases
HSF4, normal HSF4 expression and functions need to be precisely maintained throughout the lens development process
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. It is vital for them to mount appropriate responses and adapt to these stresses in order to maintain proper cellular homeostasis and functions [1] One of these responses include the activation of stress-associated responsive programs such as the heat shock response (HSR) [2], DNA damage response (DDR) [3], unfolded protein response (UPR) [4], hypoxic stress response [5], and oxidative stress response [6]. The cellular heat shock response program is tightly governed by a family of transcription factors known as the heat shock factors (HSFs). Like most cellular and molecular processes,activation the activation of HSR is tightly ulated by a specific transcription factor family known as heat shock factors (HSFs). The molecular properties and roles of HSF4 in physiological and pathophysiological processes will be discussed in the subsequent sections
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