Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down-regulates its enzymatic activity

Genes Cells. 2014 Oct;19(10):766-77. doi: 10.1111/gtc.12176. Epub 2014 Sep 8.

Abstract

Substantially high rate of glycolysis, known as the Warburg effect, is a well-known feature of cancers, and emerging evidence suggests that it supports cancerous proliferation/tumor growth. Phosphoglycerate mutase (PGAM), a glycolytic enzyme, is commonly up-regulated in several cancers, and recent reports show its involvement in the Warburg effect. Here, a comprehensive analysis shows that PGAM is acetylated at lysines 100/106/113/138 in its central region, and a member of the Sirtuin family (class III deacetylase), SIRT2, is responsible for its deacetylation. Over-expression of SIRT2 or mutations at the acetylatable lysines of PGAM attenuates cancer cell proliferation with a concomitant decrease in PGAM activity. We also report that the acetyltransferase PCAF (p300/CBP-associated factor) interacts with PGAM and acetylates its C-terminus, but not the central region. As prior evidence suggests that SIRT2 functions as a tumor suppressor, our results would provide support for the mechanistic basis of this activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Arginine / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Humans
  • Lysine / metabolism
  • Mice
  • Mutation
  • Phosphoglycerate Mutase / metabolism*
  • Protein Structure, Tertiary
  • Sirtuin 2 / genetics
  • Sirtuin 2 / metabolism*
  • Sirtuins / metabolism
  • p300-CBP Transcription Factors / metabolism*

Substances

  • Arginine
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • SIRT2 protein, human
  • Sirtuin 2
  • Sirtuins
  • Phosphoglycerate Mutase
  • Lysine