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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.
Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma.
Citation | “Pyruvate Kinase M2 Interacts With Nuclear Sterol Regulatory Element-Binding Protein 1A And Thereby Activates Lipogenesis And Cell Proliferation In Hepatocellular Carcinoma.”. The Journal Of Biological Chemistry, pp. 6623-6634. . |
Center | Albert Einstein College of Medicine |
Author | Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang |
Keywords | PKM2, SREBP-1a, cell proliferation, gene transcription, Hepatocellular carcinoma, lipid metabolism, lipid synthesis, lipogenesis, Liver cancer, pyruvate kinase, sterol regulatory element–binding protein |
Abstract |
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 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. |
Year of Publication |
2018
|
Journal |
The Journal of biological chemistry
|
Volume |
293
|
Issue |
17
|
Number of Pages |
6623-6634
|
Date Published |
12/2018
|
ISSN Number |
1083-351X
|
DOI |
10.1074/jbc.RA117.000100
|
Alternate Journal |
J. Biol. Chem.
|
PMID |
29514980
|
PMCID |
PMC5925817
|
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