气候变化领域集成服务门户(CCPortal): ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor

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DOI	10.1073/pnas.2019052118
	ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor–activated cancer
	Tang B.; Sun R.; Wang D.; Sheng H.; Wei T.; Wang L.; Zhang J.; Ho T.H.; Yang L.; Wei Q.; Huang H.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Both gene repressor (Polycomb-dependent) and activator (Polycomb-independent) functions of the Polycomb protein enhancer of zeste homolog 2 (EZH2) are implicated in cancer progression. EZH2 protein can be phosphorylated at various residues, such as threonine 487 (T487), by CDK1 kinase, and such phosphorylation acts as a Polycomb repressive complex 2 (PRC2) suppression “code” to mediate the gene repressor-to-activator switch of EZH2 functions. Here we demonstrate that the histone reader protein ZMYND8 is overexpressed in human clear cell renal cell carcinoma (ccRCC). ZMYND8 binds to EZH2, and their interaction is largely enhanced by CDK1 phosphorylation of EZH2 at T487. ZMYND8 depletion not only enhances Polycomb-dependent function of EZH2 in hypoxia-exposed breast cancer cells or von Hippel–Lindau (VHL)-deficient ccRCC cells, but also suppresses the FOXM1 transcription program. We further show that ZMYND8 is required for EZH2–FOXM1 interaction and is important for FOXM1-dependent matrix metalloproteinase (MMP) gene expression and EZH2-mediated migration and invasion of VHL-deficient ccRCC cells. Our results identify a previously uncharacterized role of the chromatin reader ZMYND8 in recognizing the PRC2-inhibitory phosphorylation “code” essential for the Polycomb-dependent to -independent switch of EZH2 functions. They also reveal an oncogenic pathway driving cell migration and invasion in hypoxia-inducible factor–activated (hypoxia or VHL-deficient) cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cancer; EZH2; Hypoxia; PRC2; ZMYND8
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180552
作者单位	Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, United States; Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, United States; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Scottsdale, AZ 85259, United States; Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Phoenix, AZ 85054, United States; Department of Urology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, United States; Mayo Clinic Cancer Center, Mayo Clinic College of Medicine and Science, Roch...
推荐引用方式 GB/T 7714	Tang B.,Sun R.,Wang D.,等. ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor–activated cancer[J],2021,118(8).
APA	Tang B..,Sun R..,Wang D..,Sheng H..,Wei T..,...&Huang H..(2021).ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor–activated cancer.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Tang B.,et al."ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor–activated cancer".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).