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Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma

文献类型：期刊论文

作者Zhao, Xiaoping2; Zhao, Li2; Li, Jiajin2; Min, Xuejie2; Liu, Jianjun2; Huang, Gang2,3; Yang, Hao3; Yang, Fajun1; ,
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2018
卷号293期号:17页码:6623-6634
ISSN号0021-9258
关键词lipid metabolism gene transcription hepatocellular carcinoma lipid synthesis lipogenesis cell proliferation liver cancer pyruvate kinase PKM2 SREBP-1a sterol regulatory element-binding protein
DOI10.1074/jbc.RA117.000100
文献子类Article
英文摘要Dysregulation of lipid metabolism is common in cancer cells, but the underlying mechanisms are poorly understood. Sterol regulatory element-binding proteins (SREBPs) stimulate lipid biosynthesis through transcriptional activation of lipogenic enzymes. However, SREBPs' roles and potential interacting partners in cancer cells are not fully defined. Using a biochemical approach, we found here that pyruvate kinase M2 (PKM2) physically interacts with the nuclear form of SREBP-1a (nBP1a), by binding to amino acids 43-56 in nBP1a. We also found that PKM2 activates SREBP target gene expression and lipid biosynthesis by stabilizing nBP1a proteins. Using a competitive peptide inhibitor to block the formation of the SREBP-1a/PKM2 complex, we observed that this blockade inhibited lipogenic gene expression. Of note, nBP1a phosphorylation at Thr-59 enhanced the binding to PKM2 and promoted cancer cell growth. Moreover, we show that PKM2 phosphorylates Thr-59 in vitro. Lastly, in human patients with hepatocellular carcinoma, nBP1a phosphorylation at Thr-59 was negatively correlated with clinical outcomes. Together, our results reveal that nBP1a/PKM2 interaction activates lipid metabolism genes in cancer cells and that Thr-59 phosphorylation of SREBP-1a plays an important role in cancer cell proliferation.
学科主题Biochemistry & Molecular Biology
WOS关键词LIPID-METABOLISM ; GENE-TRANSCRIPTION ; CANCER-CELLS ; TUMOR-GROWTH ; TUMORIGENESIS ; PATHWAY ; EXPRESSION ; PROGNOSIS ; ISOFORM ; SREBP1
语种英语
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号WOS:000431108600032
版本出版稿
源URL[http://202.127.25.144/handle/331004/710]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Albert Einstein Coll Med, Dept Med & Dev & Mol Biol, New York, NY 10461 USA,
2.Shanghai Jiao Tong Univ, Dept Nucl Med, Ren Ji Hosp, Sch Med, Shanghai 200127, Peoples R China;
3.Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai Inst Biol Sci,Chinese Acad Sci, Shanghai 200025, Peoples R China;
推荐引用方式
GB/T 7714		 Zhao, Xiaoping,Zhao, Li,Li, Jiajin,et al. Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(17):6623-6634.
APA Zhao, Xiaoping.,Zhao, Li.,Li, Jiajin.,Min, Xuejie.,Liu, Jianjun.,...&,.(2018).Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma.JOURNAL OF BIOLOGICAL CHEMISTRY,293(17),6623-6634.
MLA Zhao, Xiaoping,et al."Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma".JOURNAL OF BIOLOGICAL CHEMISTRY 293.17(2018):6623-6634.

入库方式： OAI收割

来源：上海营养与健康研究所

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