Nuclear PKM2 regulates the Warburg effect

作者：Yang Weiwei; Lu Zhimin^*

来源：Cell Cycle, 2013, 12(19): 3154-3158.

DOI：10.4161/cc.26182

• PKM2
• PKM1
• ERK
• histone
• c-Myc
• cyclin D1
• the Warburg effect

Pyruvate kinase is a rate-limiting glycolytic enzyme. The PKM1 and PKM2 isoforms result from mutually exclusive alternative splicing of the PKM pre-mRNA. PKM2 rather than PKM1 regulates the Warburg effect and tumorigenesis by poorly understood mechanisms. Emerging evidence has revealed that ERK1/2 phosphorylates PKM2, but not PKM1, leading to PIN1-dependent cis-trans isomerization and conversion of PKM2 from a tetramer to a monomer. Monomeric PKM2 translocates into the nucleus, where it functions as a histone kinase and upregulates the expression of c-Myc and cyclin D1, thereby promoting the Warburg effect and cell cycle progression, respectively. Thus, nuclear PKM2 is essential for tumorigenesis and may serve as a target for treating human cancer.

• 出版日期2013-10-1