MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment

doi:10.1093/jmcb/mjaa038

	MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment
	Wang, Bing 1,2,3,4; Lim, Chuan-Bian 4; Yan, Jiawei4,5 ; Li, Lizhen 4; Wang, Jufang 1,2; Little, John B.4; Yuan, Zhi-Min 4
	2020-09
发表期刊	JOURNAL OF MOLECULAR CELL BIOLOGY (IF:5.3[JCR-2023],6.1[5-Year])
ISSN	1674-2788
卷号	12 期号:9 页码:713-722
发表状态	已发表
DOI	10.1093/jmcb/mjaa038
摘要	A role of tumor-suppressive activity of p53 in the tumor microenvironment (TME) has been implicated but remains fairly understudied. To address this knowledge gap, we leveraged our Mdmx(S314A) mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor progression. We found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent manner. As a result, an immunosuppressive TME was developed, as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 polarization. Remarkably, ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells, which was associated with mitigation of immunosuppression and significant tumor growth delay. Our data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment, suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.
关键词	p53 MDMX tumor microenvironment immune cell infiltration macrophage polarization
收录类别	SCI ; SCIE
语种	英语
资助项目	National Cancer Institute at the National Institutes of Health[R01CA233558][R01CA167814][R01CA125144]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000605614800005
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125028
专题	生命科学与技术学院_PI研究组_洪诗雅组
通讯作者	Yuan, Zhi-Min
作者单位	1.Chinese Acad Sci, Key Lab Space Radiobiol Gansu Prov, Inst Modern Phys, Lanzhou, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Inst Modern Phys, Lanzhou, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Harvard TH Chan Sch Publ Hlth, John B Little Ctr Radiat Sci, Boston, MA 02115 USA 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Bing,Lim, Chuan-Bian,Yan, Jiawei,et al. MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2020,12(9):713-722.
APA	Wang, Bing.,Lim, Chuan-Bian.,Yan, Jiawei.,Li, Lizhen.,Wang, Jufang.,...&Yuan, Zhi-Min.(2020).MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.JOURNAL OF MOLECULAR CELL BIOLOGY,12(9),713-722.
MLA	Wang, Bing,et al."MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment".JOURNAL OF MOLECULAR CELL BIOLOGY 12.9(2020):713-722.