Characterization of HSF1 Interactome during Anisomelic Acid Treatment Using TurboID Proximal Labeling
Year: 2023
Type: dissertation
Abstract: The heat shock response involves the expression of molecular chaperones that aid in re-folding or degradation of proteins in physiological and pathological conditions that promote accumulation of misfolded proteins. A key regulator of the heat shock response is heat shock factor 1 (HSF1), which induces the expression of molecular chaperones. HSF1 is deregulated in several cancers, as it supports various facets of malignancy. Unpublished results from the Sistonen laboratory have shown that treatment with anisomelic acid (AA), a compound with cytotoxicity against cervical carcinomas, can reduce the expression of HSF1 and HSF2. However, the mechanism behind the AA-mediated downregulation remains elusive. Initially, immunofluorescence imaging was performed to determine the subcellular location of HSF1 and HSF2 during AA treatment. The results revealed that HSF1 and HSF2 accumulate into nuclear condensates upon AA treatment in a cell line-dependent manner. Moreover, TurboID-mediated proximal labeling coupled with mass spectrometry was implemented to identify the protein interactions that regulate HSF1 expression during treatment with AA. Several previously identified protein interactions were identified, and the AA-dependent protein interactors were mainly involved in chromatin remodeling, mRNA-processing, heat shock, and apoptosis. Overall, these results suggest that AA treatment causes HSF1 to associate with protein complexes involved in RNA polymerase II-mediated transcription and shed light on cellular components that may regulate the stability and activity of HSF1 during treatment with AA.
Source: Doria (University of Helsinki)
Author: Roininen, Jannica
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7115216730