Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down‐regulates its enzymatic activity. (8th September 2014)

• Record Type: Journal Article
• Authors: Tsusaka, Takeshi; Guo, Tingting; Yagura, Teiti; Inoue, Toshiaki; Yokode, Masayuki; Inagaki, Nobuya; Kondoh, Hiroshi
• Is Part Of: Genes to cells. Volume 19:Number 10(2014:Oct.)
• Page Start: 766
• Page End: 777
• Publication Date: 2014-09-08
• Subjects: Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12176
• Languages: English
• ISSNs: 1356-9597

Abstract

<abstract abstract-type="main" id="gtc12176-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>