1. A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires.
- Author
-
Begitt A, Krause S, Cavey JR, Vinkemeier DE, and Vinkemeier U
- Subjects
- Cytokines metabolism, Phosphorylation, STAT1 Transcription Factor genetics, STAT1 Transcription Factor metabolism, STAT2 Transcription Factor genetics, STAT2 Transcription Factor metabolism, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, STAT4 Transcription Factor genetics, STAT4 Transcription Factor metabolism, STAT5 Transcription Factor genetics, STAT5 Transcription Factor metabolism, Protein Multimerization, Gene Expression Regulation, Trans-Activators metabolism, STAT Transcription Factors genetics, STAT Transcription Factors metabolism
- 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., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF