Proteomic profiling identifies a direct interaction between heat shock transcription factor 2 and the focal adhesion adapter talin‐1 - UTU Research Portal

A1 Refereed original research article in a scientific journal

Proteomic profiling identifies a direct interaction between heat shock transcription factor 2 and the focal adhesion adapter talin‐1

Authors: Da Silva, Alejandro J.; Hästbacka, Hendrik S. E.; Luoto, Jens C.; Gough, Rosemarie E.; Coelho-Rato, Leila S.; Laitala, Leena M.; Goult, Benjamin T.; Imanishi, Susumu Y.; Sistonen, Lea; Henriksson, Eva

Publisher: Wiley-Blackwell

Publishing place: HOBOKEN

Publication year: 2024

Journal: FEBS Journal

Journal name in source: The FEBS Journal

Journal acronym: FEBS J

Volume: 291

Issue: 21

First page : 4830

Last page: 4848

Number of pages: 19

ISSN: 1742-464X

eISSN: 1742-4658

DOI: https://doi.org/10.1111/febs.17271

Web address : http://dx.doi.org/10.1111/febs.17271

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/458296546

Abstract

Heat shock factor 2 (HSF2) is a versatile transcription factor that regulates gene expression under stress conditions, during development, and in disease. Despite recent advances in characterizing HSF2-dependent target genes, little is known about the protein networks associated with this transcription factor. In this study, we performed co-immunoprecipitation coupled with mass spectrometry analysis to identify the HSF2 interactome in mouse testes, where HSF2 is required for normal sperm development. Endogenous HSF2 was discovered to form a complex with several adhesion-associated proteins, a finding substantiated by mass spectrometry analysis conducted in human prostate carcinoma PC-3 cells. Notably, this group of proteins included the focal adhesion adapter protein talin-1 (TLN1). Through co-immunoprecipitation and proximity ligation assays, we demonstrate the conservation of the HSF2-TLN1 interaction from mouse to human. Additionally, employing sequence alignment analyses, we uncovered a TLN1-binding motif in the HSF2 C terminus that binds directly to multiple regions of TLN1 in vitro. We provide evidence that the 25 C-terminal amino acids of HSF2, fused to EGFP, are sufficient to establish a protein complex with TLN1 and modify cell-cell adhesion in human cells. Importantly, this TLN1-binding motif is absent in the C-terminus of a closely related HSF family member, HSF1, which does not form a complex with TLN1. These results highlight the unique molecular characteristics of HSF2 in comparison to HSF1. Taken together, our data unveil the protein partners associated with HSF2 in a physiologically relevant context and identifies TLN1 as the first adhesion-related HSF2-interacting partner.

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Funding information in the publication:
This work has been funded by the Academy of Finland (LS); Sigrid Juselius Foundation (LS), Centre for International Mobility (AJDS, EH); Finnish Cultural Foundation (AJDS); K. Albin Johansson Foundation (AJDS, EH); Magnus Ehrnrooth's Foundation (AJDS, EH); Medicinska Understödsföreningen Liv och Hälsa r.f. (AJDS, JCL, EH); Otto A. Malm Foundation (AJDS), The Maud Kuistila Memorial Foundation (HSEH), Ella ja Georg Ehrnrooth's Foundation (HSEH, JCL), Victoriastiftelsen (JCL), Svenska Kulturfonden (JCL).