Comparative interactomes of HSF1 in stress and disease reveal a role for CTCF in HSF1-mediated gene regulation.

Abstract

Heat shock transcription factor 1 (HSF1) orchestrates cellular stress protection by activating or repressing gene transcription in response to protein misfolding, oncogenic cell proliferation, and other environmental stresses. HSF1 is tightly regulated via intramolecular repressive interactions, post-translational modifications, and protein-protein interactions. How these HSF1 regulatory protein interactions are altered in response to acute and chronic stress is largely unknown. To elucidate the profile of HSF1 protein interactions under normal growth and chronic and acutely stressful conditions, quantitative proteomics studies identified interacting proteins in the response to heat shock or in the presence of a poly-glutamine aggregation protein cell-based model of Huntington's disease. These studies identified distinct protein interaction partners of HSF1 as well as changes in the magnitude of shared interactions as a function of each stressful condition. Several novel HSF1-interacting proteins were identified that encompass a wide variety of cellular functions, including roles in DNA repair, mRNA processing, and regulation of RNA polymerase II. One HSF1 partner, CTCF, interacted with HSF1 in a stress-inducible manner and functions in repression of specific HSF1 target genes. Understanding how HSF1 regulates gene repression is a crucial question, given the dysregulation of HSF1 target genes in both cancer and neurodegeneration. These studies expand our understanding of HSF1-mediated gene repression and provide key insights into HSF1 regulation via protein-protein interactions.

• Authors: Eileen T Burchfiel, Anniina Vihervaara, Michael J Guertin, Rocio Gomez-Pastor, Dennis J Thiele
• Journal: The Journal of biological chemistry (J Biol Chem) 2021 Jan-Jun Vol. 296 Pg. 100097 ISSN: 1083-351X [Electronic] United States
• PMID: 33208463 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• CCCTC-Binding Factor
• CTCF protein, human
• Ctcf protein, mouse
• HSF1 protein, human
• Heat Shock Transcription Factors
• Hsf1 protein, mouse
• Neoplasm Proteins

Topics

• Animals
• CCCTC-Binding Factor (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Heat Shock Transcription Factors (genetics, metabolism)
• Heat-Shock Response
• Humans
• Huntington Disease (genetics, metabolism, pathology)
• Mice
• Mice, Knockout
• Neoplasm Proteins (genetics, metabolism)
• Neoplasms (genetics, metabolism, pathology)
• Protein Interaction Maps