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Epigenetic Component p66a Modulates Myeloid-Derived Suppressor Cells by Modifying STAT3
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 198(7)
- Publication Year :
- 2016
-
Abstract
- STAT3 plays a critical role in myeloid-derived suppressor cell (MDSC) accumulation and activation. Most studies have probed underlying mechanisms of STAT3 activation. However, epigenetic events involved in STAT3 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 STAT3 in functional MDSCs, by using immunoprecipitation and mass spectrometry. p66a could regulate the phosphorylation and ubiquitination of STAT3. Silencing p66a promoted not only phosphorylation but also K63 ubiquitination of STAT3 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 STAT3 to suppress its activity through posttranslational modification, which reveals a novel regulatory mechanism controlling STAT3 activation during myeloid cell differentiation.
- Subjects :
- 0301 basic medicine
STAT3 Transcription Factor
Cellular differentiation
Immunology
Real-Time Polymerase Chain Reaction
Mass Spectrometry
Epigenesis, Genetic
03 medical and health sciences
Mice
Myeloid Cell Differentiation
Immunology and Allergy
Gene silencing
Animals
Immunoprecipitation
Epigenetics
Phosphorylation
STAT3
Regulation of gene expression
Mice, Inbred BALB C
biology
Myeloid-Derived Suppressor Cells
Ubiquitination
Cell Differentiation
Neoplasms, Experimental
Flow Cytometry
Mice, Inbred C57BL
030104 developmental biology
Gene Expression Regulation
Gene Knockdown Techniques
biology.protein
Myeloid-derived Suppressor Cell
Cancer research
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 198
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....a12a910d55d6dcaf3ef5cc0f30651463