Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT 2 down‐regulates its enzymatic activity

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 19; no. 10; pp. 766 - 777
• Main Authors: Tsusaka, Takeshi, Guo, Tingting, Yagura, Teiti, Inoue, Toshiaki, Yokode, Masayuki, Inagaki, Nobuya, Kondoh, Hiroshi
• Format: Journal Article
• Language: English
• Published: 01-10-2014
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12176

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),
SIRT
2, is responsible for its deacetylation. Over‐expression of
SIRT
2 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
SIRT
2 functions as a tumor suppressor, our results would provide support for the mechanistic basis of this activity.