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

Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)6623-6634
Number of pages12
JournalJournal of Biological Chemistry
Volume293
Issue number17
DOIs
StatePublished - Jan 1 2018

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Sterol Regulatory Element Binding Protein 1
Lipogenesis
Pyruvate Kinase
Cell proliferation
Hepatocellular Carcinoma
Sterol Regulatory Element Binding Proteins
Cell Proliferation
Phosphorylation
Biosynthesis
Cells
Lipid Metabolism
Gene expression
Neoplasms
Lipids
Gene Expression
Neoplasm Genes
Cell growth
Transcriptional Activation
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pyruvate kinase M2 interacts with nuclear sterol regulatory element– binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma. / Zhao, Xiaoping; Zhao, Li; Yang, Hao; Li, Jiajin; Min, Xuejie; Yang, Fajun; Liu, Jianjun; Huang, Gang.

In: Journal of Biological Chemistry, Vol. 293, No. 17, 01.01.2018, p. 6623-6634.

Research output: Contribution to journalArticle

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AU - Liu, Jianjun

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