The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration.

ABSTRACT: Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-dependent regulator of multiple pathways, its role in Rac1 activation has not been reported. Similarly, SIRT2 has been demonstrated to be upregulated in some cancers; however, studies have also reported its role in tumor suppression. Here, we demonstrate that SIRT1 and SIRT2 positively regulate the levels of Rac1-GTP and the activity of T-cell lymphoma invasion and metastasis 1 (TIAM1), a Rac guanine nucleotide exchange factor (GEF). Transient inhibition of SIRT1 and SIRT2 resulted i

SUBMITTER: Saxena M 

PROVIDER: S-EPMC4067478 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature