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PKC-mediated phosphorylation of BCL11B at Serine 2 negatively regulates its interaction with NuRD complexes during CD4+ T cell activation


Dubuissez M et al.

The transcription factor BCL11B/CTIP2 is a major regulatory protein implicated in various aspects of development, function and survival of T cells. MAPK-mediated phosphorylation and SUMOylation modulate BCL11B transcriptional activity, switching it from a repressor in naïve 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 PKC-mediated phosphorylation of BCL11B Ser2 does not significantly impact on BCL11B SUMOylation but negatively regulates NuRD recruitment by dampening the interaction with 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 IL2 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 post-translational modification linking PKC signalling pathway to 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.

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Antibody

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Published
May, 2016

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  • Antibody ChIP icon
    C15200206
    RbAp48 Antibody

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