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

ABSTRACT: The conversion of STAT proteins from latent to active transcription factors is central to cytokine signalling. 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-localisation-based assay and tested all 28 possible combinations of the seven unphosphorylated STAT proteins in living cells. It led to the identification of five U-STAT homodimers ―STAT1, STAT3, STAT4, STAT5A and STAT5B― and two heterodimers ―STAT1:STAT2 and STAT5A:STAT5B― as well as semi-quantitative assessments of the forces and characterisations 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.

SUBMITTER:  

PROVIDER: S-BIAD669 | bioimages |

REPOSITORIES: bioimages