Susan Kane

Regulation of WRN protein cellular localization and enzymatic activities by SIRT1 mediated deacetylation

Werner syndrome is an autosomal recessive disorder associated with premature aging and cancer predisposition caused by mutations of the WRN gene. WRN is a member of the RecQ DNA helicase family with functions in maintaining genome stability. Sir2, an NAD-dependent histone deacetylase, has been proven to extend life span in yeast and Caenorhabditis elegans. Mammalian Sir2 (SIRT1) has also been found to regulate premature cellular senescence induced by the tumor suppressors PML and p53. SIRT1 plays an important role in cell survival promoted by calorie restriction. Here we show that SIRT1 interacts with WRN both in vitro and in vivo; this interaction is enhanced after DNA damage. WRN can be acetylated by acetyltransferase CBP/p300, and SIRT1 can deacetylate WRN both in vitro and in vivo. WRN acetylation decreases its helicase and exonuclease activities, and SIRT1 can reverse this effect. WRN acetylation alters its nuclear distribution. Down-regulation of SIRT1 reduces WRN translocation from nucleoplasm to nucleoli after DNA damage. These results suggest that SIRT1 regulates WRN-mediated cellular responses to DNA damage through deacetylation of WRN.

Hormonal regulation of the insulin-responsive glucose transporter, GLUT4: some recent advances.

gradient chimique a travers la membrane de la cellule. I1 est possible de proposer une explication cette diversit6 d’expression basee sur l’analyse des proprietes cinetiques et fonctionnelles de ces diffirents isoformes. Ainsi, on pense que GLUT1 est impliquC dans le transport du glucose 2 travers les barrikres entre le sang et les organes tels que la rCtine, et a travers la barrih-e entre le sang et le cerveau; il est aussi impliquC dans le maintien de niveaux basals ou d’entretien de I’activitC de transport du glucose dans beaucoup de types de cellules, sinon dans tous. GLUT;! est un transporteur a haute capacitC et