Open AccessCan asymmetric post‐translational modifications regulate the behavior of STAT3 homodimers?
Author(s) -
LetraVilela Ricardo,
Cardoso Beatriz,
SilvaAlmeida Catarina,
Maia Rocha Ana,
Murtinheira Fernanda,
BrancoSantos Joana,
Rodriguez Carmen,
Martin Vanesa,
SantaMarta Mariana,
Herrera Federico
Publication year - 2020
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2019-00049
Subject(s) - stat3 , microbiology and biotechnology , stat protein , protein–protein interaction , signal transduction , chemistry , transcription factor , complementation , transcription (linguistics) , biology , mutant , biochemistry , gene , linguistics , philosophy
Signal transducer and activator of transcription 3 (STAT3) is a ubiquitous and pleiotropic transcription factor that plays essential roles in normal development, immunity, response to tissue damage and cancer. We have developed a Venus‐STAT3 bimolecular fluorescence complementation assay that allows the visualization and study of STAT3 dimerization and protein‐protein interactions in living cells. Inactivating mutations on residues susceptible to post‐translational modifications (PTMs) (K49R, K140R, K685R, Y705F and S727A) changed significantly the intracellular distribution of unstimulated STAT3 dimers when the dimers were formed by STAT3 molecules that carried different mutations (ie they were “asymmetric”). Some of these asymmetric dimers changed the proliferation rate of HeLa cells. Our results indicate that asymmetric PTMs on STAT3 dimers could constitute a new level of regulation of STAT3 signaling. We put forward these observations as a working hypothesis, since confirming the existence of asymmetric STAT3 homodimers in nature is extremely difficult, and our own experimental setup has technical limitations that we discuss. However, if our hypothesis is confirmed, its conceptual implications go far beyond STAT3, and could advance our understanding and control of signaling pathways.