MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function

Autor: Yuan Xiang, Jun Wang, Jia Peng Li, Wei Guo, Feng Huang, Hui Min Zhang, Han Han Li, Zhou Tong Dai, Zi Jian Zhang, Hui Li, Le Yuan Bao, Chao Jiang Gu, Kun Chen, Tong Cun Zhang, Xing Hua Liao
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-13 (2020)
Druh dokumentu: article
ISSN: 1478-811X
DOI: 10.1186/s12964-020-00574-1
Popis: Abstract Background Foxp3+CD4+ regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells. Methods The CD3+T cell and Foxp3+CD4+ regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry. Results However, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein–protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b–MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP). Conclusions Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. Video abstract
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje