1. Academic Validation
  2. Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization

Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization

  • Mol Cell. 2013 Nov 7;52(3):340-52. doi: 10.1016/j.molcel.2013.09.004.
Lei Lv 1 Yan-Ping Xu Di Zhao Fu-Long Li Wei Wang Naoya Sasaki Ying Jiang Xin Zhou Ting-Ting Li Kun-Liang Guan Qun-Ying Lei Yue Xiong
Affiliations

Affiliation

  • 1 Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China; Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China; School of Life Sciences, Fudan University 200032, People's Republic of China.
Abstract

Alternative splicing of the PKM2 gene produces two isoforms, M1 and M2, which are preferentially expressed in adult and embryonic tissues, respectively. The M2 isoform is reexpressed in human Cancer and has nonmetabolic functions in the nucleus as a protein kinase. Here, we report that PKM2 is acetylated by p300 acetyltransferase at K433, which is unique to PKM2 and directly contacts its allosteric activator, fructose 1,6-bisphosphate (FBP). Acetylation prevents PKM2 activation by interfering with FBP binding and promotes the nuclear accumulation and protein kinase activity of PKM2. Acetylation-mimetic PKM2(K433) mutant promotes cell proliferation and tumorigenesis. K433 acetylation is decreased by serum starvation and cell-cell contact, increased by cell cycle stimulation, epidermal growth factor (EGF), and oncoprotein E7, and enriched in breast cancers. Hence, K433 acetylation links cell proliferation and transformation to the switch of PKM2 from a cytoplasmic metabolite kinase to a nuclear protein kinase.

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