Targeted Replacement of HSF1 Phosphorylation Sites at S303/S307 with Alanine Residues in Mice Increases Cell Proliferation and Drug Resistance.

Abstract

Mammalian heat shock factor HSF1 transcriptional activity is controlled by a multitude of phosphorylations that occur under physiological conditions or following exposure of cells to a variety of stresses. One set of HSF1 phosphorylation is on serine 303 and serine 307 (S303/S307). These HSF1 phosphorylation sites are known to repress its transcriptional activity. Here, we describe a knock-in mouse model where these two serine residues were replaced by alanine residues and have determined the impact of these mutations on cellular proliferation and drug resistance. Our previous study using this mouse model indicated the susceptibility of the mutant mice to become obese with age due to an increase in basal levels of heat shock proteins (HSPs) and chronic inflammation. Since HSF1 transcriptional activity is increased in many tumor types, this mouse model may be a useful tool for studies related to cellular transformation and cancer.

• Authors: Xiongjie Jin, Demetrius Moskophidis, Nahid F Mivechi
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2693 Pg. 81-94 ( 2023) ISSN: 1940-6029 [Electronic] United States
• PMID: 37540428 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Transcription Factors
• DNA-Binding Proteins
• Heat Shock Transcription Factors
• Serine

Topics

• Mice
• Animals
• Transcription Factors (metabolism)
• DNA-Binding Proteins (metabolism)
• Heat Shock Transcription Factors (genetics, metabolism)
• Phosphorylation
• Drug Resistance
• Cell Proliferation
• Serine (metabolism)
• Mammals (metabolism)