A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires

Begitt, Andreas; Krause, Sebastian; Cavey, James R.; Vinkemeier, Doratha E.; Vinkemeier, Uwe

Abstract

The conversion of signal transducer and activator of transcription (STAT) proteins from latent to active transcription factors is central to cytokine signaling. Triggered by their signal-induced tyrosine phosphorylation, it is the assembly of a range of cytokine-specific STAT homo- and heterodimers that marks a key step in the transition of hitherto latent proteins to transcription activators. In contrast, the constitutive self-assembly of latent STATs and how it relates to the functioning of activated STATs is understood less well. To provide a more complete picture, we developed a co-localization-based assay and tested all 28 possible combinations of the seven unphosphorylated STAT (U-STAT) proteins in living cells. We identified five U-STAT homodimers—STAT1, STAT3, STAT4, STAT5A, and STAT5B—and two heterodimers—STAT1:STAT2 and STAT5A:STAT5B—and performed semi-quantitative assessments of the forces and characterizations of binding interfaces that support them. One STAT protein—STAT6—was found to be monomeric. This comprehensive analysis of latent STAT self-assembly lays bare considerable structural and functional diversity in the ways that link STAT dimerization before and after activation.

Citation

Begitt, A., Krause, S., Cavey, J. R., Vinkemeier, D. E., & Vinkemeier, U. (2023). A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires. Journal of Biological Chemistry, 299(5), Article 104703. https://doi.org/10.1016/j.jbc.2023.104703

• Journal Article Type: Article
• Acceptance Date: Apr 6, 2023
• Online Publication Date: Apr 12, 2023
• Publication Date: 2023-05
• Deposit Date: Apr 17, 2023
• Publicly Available Date: May 11, 2023
• Journal: Journal of Biological Chemistry
• Print ISSN: 0021-9258
• Electronic ISSN: 1083-351X
• Publisher: American Society for Biochemistry and Molecular Biology
• Peer Reviewed: Peer Reviewed
• Volume: 299
• Issue: 5
• Article Number: 104703
• DOI: https://doi.org/10.1016/j.jbc.2023.104703
• Keywords: Cell Biology; Molecular Biology; Biochemistry, transcription factor, STAT1, STAT2, STAT3, STAT4, STAT5, STAT6, dimerization, translocation assay, NES, NLS
• Public URL: https://nottingham-repository.worktribe.com/output/19465598
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0021925823003459?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires; Journal Title: Journal of Biological Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jbc.2023.104703; Content Type: article; Copyright: © 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.