A Novel Role for Pyruvate Kinase M2 as a Corepressor for P53 during the DNA Damage Response in Human Tumor Cells

• DOI: 10.1074/jbc.m116.737056
• Publication Date: 2016-11-04T01:49:22Z
• Authors: Li Xia; Xin-Ran Wang; Xiao-Ling Wang; Su-Hui Liu; Xiao-Wei Ding; Guo-Qiang Chen; Ying Lu
• Keywords: PKM2; DNA-PKcs

<h2>Abstract</h2> The pyruvate kinase (PK) is a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, yielding one molecule ATP. M2 isoform PK (PKM2) predominantly expressed in normal proliferating cells and tumors, both metabolic non-metabolic activities for promoting tumor cell proliferation have been identified. However, exact roles PKM2 initiation, growth maintenance are not yet fully understood. Using immunoprecipitation-coupled LC-MS/MS MCF7 exposed DNA-damaging agent, we report that nuclear interacts directly with P53 protein, critical safeguard genome stability. Specifically, inhibits P53-dependent transactivation <i>P21</i> gene by preventing binding promoter, leading nonstop G₁ phase. As result, expression provides advantage presence DNA damage stimulus. In addition, interferes phosphorylation at serine 15, known stimulate activity ATM serine/threonine kinase. These findings reveal new role modulating response illustrate novel mechanism participating tumorigenesis.