DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism

doi:10.1186/s13072-019-0302-9

	DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism
	Chen, Ling 2,3,4,5,9; Shi, Ying 2,3,4; Liu, Na 2,3,4; Wang, Zuli 2,3,4; Yang, Rui 2,3,4; Yan, Bin 2,3,4,6; Liu, Xiaoli 2,3,4; Lai, Weiwei 2,3,4; Liu, Yating 2,3,4; Xiao, Desheng 7
刊名	EPIGENETICS & CHROMATIN
	2019-10-08
卷号	12 期号:1 页码:22
关键词	LSH P53 DUB PKM2 Lipid metabolism
DOI	10.1186/s13072-019-0302-9
通讯作者	Xia, Zanxian(xiazanxian@sklmg.edu.cn) ; Tao, Yongguang(taoyong@csu.edu.cn)
英文摘要	Background: The stability of p53 is mainly controlled by ubiquitin-dependent degradation, which is triggered by the E3 ubiquitin ligase MDM2. The chromatin modifier lymphoid-specific helicase (LSH) is essential for DNA methylation and cancer progression as a transcriptional repressor. The potential interplay between chromatin modifiers and transcription factors remains largely unknown. Results: Here, we present data suggesting that LSH regulates p53 in cis through two pathways: prevention proteasomal degradation through its deubiquitination, which is achieved by reducing the lysine 11-linked, lysine 48-linked polyubiquitin chains (K11 and K48) on p53; and revival of the transcriptional activity of p53 by forming a complex with PKM2 (pyruvate kinase 2). Furthermore, we confirmed that the LSH-PKM2 interaction occurred at the intersubunit interface region of the PKM2 C-terminal region and the coiled-coil domains (CC) and ATP-binding domains of LSH, and this interaction regulated p53-mediated transactivation in cis in lipid metabolism, especially lipid catabolism. Conclusion: These findings suggest that LSH is a novel regulator of p53 through the proteasomal pathway, thereby providing an alternative mechanism of p53 involvement in lipid metabolism in cancer.
资助项目	National Natural Science Foundation of China[81672787] ; National Natural Science Foundation of China[81874139] ; National Natural Science Foundation of China[81672991] ; National Natural Science Foundation of China[U1603126] ; National Natural Science Foundation of China[81872285] ; National Natural Science Foundation of China[81422051] ; National Natural Science Foundation of China[81472593] ; National Key Research and Development Program of China[2015CB553903] ; National Key Research and Development Program of China[2016YFC1200200] ; National Key Research and Development Program of China[2016YFD0500300] ; State Key Laboratory of Proteomics[SKLP-O201805]
WOS关键词	PYRUVATE-KINASE M2 ; LYMPHOID-SPECIFIC HELICASE ; GENE-TRANSCRIPTION ; REGULATES P53 ; CANCER ; PKM2 ; STABILITY ; DEGRADATION ; EXPRESSION ; TARGET
WOS研究方向	Genetics & Heredity
语种	英语
出版者	BMC
WOS记录号	WOS:000496989300002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281790]
专题	中国科学院上海药物研究所
通讯作者	Xia, Zanxian; Tao, Yongguang
作者单位	1.Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410078, Hunan, Peoples R China 2.Cent S Univ, Xiangya Hosp, Dept Pathol, Key Lab Carcinogenesis & Canc Invas,Minist Educ, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China 3.Cent S Univ, Canc Res Inst, NHC Key Lab Carcinogenesis, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China 4.Cent S Univ, Sch Basic Med, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China 5.Cent S Univ, Xiangya Hosp 2, Dept Thorac Surg, Changsha, Hunan, Peoples R China 6.Cent S Univ, Inst Med Sci, Xiangya Hosp, Dept Oncol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China 7.Cent S Univ, Xiangya Hosp, Dept Pathol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zu Chongzhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 9.Cent S Univ, Sch Life Sci, Dept Cell Biol, Changsha, Hunan, Peoples R China 10.Cent S Univ, Sch Life Sci, Hunan Key Lab Anim Models Human Dis, Changsha, Hunan, Peoples R China
推荐引用方式 GB/T 7714	Chen, Ling,Shi, Ying,Liu, Na,et al. DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism[J]. EPIGENETICS & CHROMATIN,2019,12(1):22.
APA	Chen, Ling.,Shi, Ying.,Liu, Na.,Wang, Zuli.,Yang, Rui.,...&Tao, Yongguang.(2019).DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism.EPIGENETICS & CHROMATIN,12(1),22.
MLA	Chen, Ling,et al."DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism".EPIGENETICS & CHROMATIN 12.1(2019):22.