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 1,2,4,5; Lim, Chuan-Bian 4; Yan, Jiawei 3,4; Li, Lizhen 4; Wang, Jufang 2,5; Little, John B.4; Yuan, Zhi-Min 4
刊名	JOURNAL OF MOLECULAR CELL BIOLOGY
	2020-09-01
卷号	12 期号:9 页码:713-722
关键词	p53 MDMX tumor microenvironment immune cell infiltration macrophage polarization
ISSN号	1674-2788
DOI	10.1093/jmcb/mjaa038
通讯作者	Yuan, Zhi-Min(zyuan@hsph.harvard.edu)
英文摘要	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.
资助项目	Morningside Foundation ; National Cancer Institute at the National Institutes of Health[R01CA233558] ; National Cancer Institute at the National Institutes of Health[R01CA167814] ; National Cancer Institute at the National Institutes of Health[R01CA125144]
WOS关键词	SUPPRESSES P53 ; PROGRESSION ; COMPLEX ; TRP53
WOS研究方向	Cell Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000605614800005
资助机构	Morningside Foundation ; National Cancer Institute at the National Institutes of Health
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/138172]
专题	中国科学院近代物理研究所
通讯作者	Yuan, Zhi-Min
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Key Lab Space Radiobiol Gansu Prov, Inst Modern Phys, Lanzhou, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Harvard TH Chan Sch Publ Hlth, John B Little Ctr Radiat Sci, Boston, MA 02115 USA 5.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Inst Modern Phys, Lanzhou, 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.