Protein Kinase C-Mediated Phosphorylation of BCL11B at Serine 2 Negatively Regulates Its Interaction with NuRD Complexes during CD4+ T-Cell Activation.
Fiche publication
Date publication
juillet 2016
Journal
Molecular and cellular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROHR Olivier
Tous les auteurs :
Dubuissez M, Loison I, Paget S, Vorng H, Ait-Yahia S, Rohr O, Tsicopoulos A, Leprince D
Lien Pubmed
Résumé
The transcription factor BCL11B/CTIP2 is a major regulatory protein implicated in various aspects of development, function and survival of T cells. Mitogen-activated protein kinase (MAPK)-mediated phosphorylation and SUMOylation modulate BCL11B transcriptional activity, switching it from a repressor in naive murine thymocytes to a transcriptional activator in activated thymocytes. Here, we show that BCL11B interacts via its conserved N-terminal MSRRKQ motif with endogenous MTA1 and MTA3 proteins to recruit various NuRD complexes. Furthermore, we demonstrate that protein kinase C (PKC)-mediated phosphorylation of BCL11B Ser2 does not significantly impact BCL11B SUMOylation but negatively regulates NuRD recruitment by dampening the interaction with MTA1 or MTA3 (MTA1/3) and RbAp46 proteins. We detected increased phosphorylation of BCL11B Ser2 upon in vivo activation of transformed and primary human CD4(+) T cells. We show that following activation of CD4(+) T cells, BCL11B still binds to IL-2 and Id2 promoters but activates their transcription by recruiting P300 instead of MTA1. Prolonged stimulation results in the direct transcriptional repression of BCL11B by KLF4. Our results unveil Ser2 phosphorylation as a new BCL11B posttranslational modification linking PKC signaling pathway to T-cell receptor (TCR) activation and define a simple model for the functional switch of BCL11B from a transcriptional repressor to an activator during TCR activation of human CD4(+) T cells.
Mots clés
CD4-Positive T-Lymphocytes, immunology, HEK293 Cells, Histone Deacetylases, metabolism, Humans, Interleukin-2, metabolism, Jurkat Cells, Lymphocyte Activation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, metabolism, Neoplasm Proteins, metabolism, Phosphorylation, Protein Kinase C, metabolism, Repressor Proteins, chemistry, Retinoblastoma-Binding Protein 7, metabolism, Serine, metabolism, Tumor Suppressor Proteins, chemistry
Référence
Mol. Cell. Biol.. 2016 07 1;36(13):1881-98