Epigenetic Component p66a Modulates Myeloid-Derived Suppressor Cells by Modifying STAT3.

plays a critical role in myeloid-derived suppressor cell (MDSC) accumulation and activation. Most studies have probed underlying mechanisms of duanyu18133 activation. However, epigenetic events involved in duanyu18133 activation are poorly understood. In this study, we identified several epigenetic-associated proteins such as p66a (Gatad2a), a novel protein transcriptional repressor that might interact with duanyu18133 in functional MDSCs, by using immunoprecipitation and mass spectrometry. p66a could regulate the phosphorylation and ubiquitination of Silencing p66a promoted not only phosphorylation but also K63 ubiquitination of duanyu18133 in the activated MDSCs. Interestingly, p66a expression was significantly suppressed by IL-6 both in vitro and in vivo during MDSC activation, suggesting that p66a is involved in IL-6-mediated differentiation of MDSCs. Indeed, silencing p66a could promote MDSC accumulation, differentiation, and activation. Tumors in mice injected with p66a small interfering RNA-transfected MDSCs also grew faster, whereas tumors in mice injected with p66a-transfected MDSCs were smaller as compared with the control. Thus, our data demonstrate that p66a may physically interact with duanyu18133 to suppress its activity through posttranslational modification, which reveals a novel regulatory mechanism controlling duanyu18133 activation during myeloid cell differentiation.

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