REVIEW article
Front. Mol. Biosci.
Sec. Cellular Biochemistry
The role of bHLH-PAS transcription factors in endoplasmic reticulum stress
Provisionally accepted
- 1Wroclaw Medical University, Wrocław, Poland
- 2Politechnika Wroclawska, Wrocław, Poland
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The bHLH-PAS protein family consists of transcription factors that are involved in the regulation of key physiological processes such as the response to hypoxia, circadian rhythms, the detoxification of xenobiotics, and metabolic homeostasis. These proteins act as environmental sensors, integrating diverse signals into transcriptional responses. In recent years, increasing attention has been paid to their role in regulating endoplasmic reticulum stress (ER stress), which is an adaptive cellular response to disturbances in protein-folding. Prolonged or severe ER stress can activate the unfolded protein response (UPR) and apoptotic pathways, contributing to the development of numerous disorders, including neurodegenerative, cancerous, and inflammatory diseases. This review focuses on the functions of bHLH-PAS proteins, such as AHR, HIF, SIM, NPAS1-4, and CLOCK, with particular emphasis on their potential role in modulating ER stress. Molecular mechanisms through which these proteins regulate responses to hypoxia and other cellular stressors are also discussed, with a focus on their importance in maintaining homeostasis and their potential as therapeutic targets.
Keywords: bHLH-PAS domain proteins, transcriptional factors, Endoplasmic Reticulum Stress, cellularstress, therapeutic targets
Received: 22 Oct 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Krauze, Krzystek-Korpacka, Maciejewska and Greb-Markiewicz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Izabela Krauze
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