Mitogenic and Oncogenic Stimulation of K433 Acetylation Promotes PKM2 Protein Kinase Activity and Nuclear Localization

被引：352

作者：

Lv, Lei ^{[1
,2
,3
,4
]}

Xu, Yan-Ping ^{[1
,2
,3
,4
]}

Zhao, Di ^{[1
,2
,3
]}

Li, Fu-Long ^{[1
,2
,3
,4
]}

Wang, Wei ^{[6
,7
]}

Sasaki, Naoya ^{[8
]}

Jiang, Ying ^{[5
]}

Zhou, Xin ^{[1
,2
,3
,4
]}

Li, Ting-Ting ^{[1
,2
,3
,4
]}

Guan, Kun-Liang ^{[6
,7
]}

Lei, Qun-Ying ^{[1
,2
,3
]}

Xiong, Yue ^{[4
,8
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Key Lab Mol Med, Minist Educ, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China

[3] Fudan Univ, Inst Biomed Sci, Mol & Cell Biol Lab, Shanghai 200032, Peoples R China

[4] Fudan Univ, Sch Life Sci, Shanghai 200032, Peoples R China

[5] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai 200032, Peoples R China

[6] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

来源：

MOLECULAR CELL | 2013年 / 52卷 / 03期

关键词：

RAT PYRUVATE-KINASE; TUMOR-GROWTH; LYSINE ACETYLATION; ALLOSTERIC REGULATION; GENE-TRANSCRIPTION; THYROID-HORMONE; BINDING PROTEIN; M2; FRUCTOSE-1,6-BISPHOSPHATE; TUMORIGENESIS;

D O I：

10.1016/j.molcel.2013.09.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：340 / 352

页数：13

共 29 条

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Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis [J].