Phosphoproteomic analysis reveals an intrinsic pathway for histone deacetylase 7 regulation that controls cytotoxic T lymphocyte function

The present study reports an unbiased analysis of cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified were transcription activators, co-repressors and chromatin regulators. A focus on chromatin regulators revealed that CTLs have high expression of histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.