Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine

doi:10.1172/JCI146187

	Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine
	Zhang, Yajuan 1; Yu, Hua 2; Zhang, Jie3 ; Gao, Hong 1; Wang, Siyao 1; Li, Shuxian3 ; Wei, Ping 4; Liang, Ji 1; Yu, Guanzhen 5; Wang, Xiongjun 2; Li, Xinxiang 6; Li, Dawei 6; Yang, Weiwei 1,7
	2021-11-01
发表期刊	JOURNAL OF CLINICAL INVESTIGATION
ISSN	0021-9738
EISSN	1558-8238
卷号	131 期号:21
DOI	10.1172/JCI146187
摘要	Although serine metabolism plays a crucial role in the proliferation and survival of tumor cells, how it supports tumor cell migration remains poorly understood. Phosphoglycerate dehydrogenase (PHGDH) catalyzes the oxidation of 3-phosphoglycerate to 3-phosphonooxypyruvate, the first committed step in de novo serine biosynthesis. Here we show that PHGDH was monoubiquitinated by cullin 4A-based E3 ligase complex at lysine 146 in colorectal cancer (CRC) cells, which enhanced PHGDH activity by recruiting a chaperone protein, DnaJ homolog subfamily A member 1, to promote its tetrameric formation, thereby increasing the levels of serine, glycine, and S-adenosylmethionine (SAM). Increased levels of SAM upregulated the expression of cell adhesion genes (laminin subunit gamma 2 and cysteine rich angiogenic inducer 61) by initiating SET domain containing 1A-mediated trimethylation of histone H3K4, thereby promoting tumor cell migration and CRC metastasis. Intriguingly, SAM levels in tumors or blood samples correlated with the metastatic recurrence of patients with CRC. Our finding not only reveals a potentially new role and mechanism of SAM-promoted tumor metastasis but also demonstrates a regulatory mechanism of PHGDH activity by monoubiquitination.
URL	查看原文
收录类别	SCIE
语种	英语
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000715042800005
出版者	AMER SOC CLINICAL INVESTIGATION INC
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/130316
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_高冠军组生命科学与技术学院_硕士生
通讯作者	Wang, Xiongjun; Li, Xinxiang; Li, Dawei; Yang, Weiwei
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai Key Lab Mol Androl,Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol,Ctr Excellence, Shanghai, Peoples R China; 2.Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Fudan Univ, Dept Pathol, Shanghai Canc Ctr, Shanghai, Peoples R China; 5.Chinese Acad Sci, Zhejiang Inst Digital Media, Med Artificial Intelligence Lab, Shaoxing, Peoples R China; 6.Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, Shanghai, Peoples R China; 7.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Yajuan,Yu, Hua,Zhang, Jie,et al. Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine[J]. JOURNAL OF CLINICAL INVESTIGATION,2021,131(21).
APA	Zhang, Yajuan.,Yu, Hua.,Zhang, Jie.,Gao, Hong.,Wang, Siyao.,...&Yang, Weiwei.(2021).Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.JOURNAL OF CLINICAL INVESTIGATION,131(21).
MLA	Zhang, Yajuan,et al."Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine".JOURNAL OF CLINICAL INVESTIGATION 131.21(2021).