Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro.

ABSTRACT: Our work suggests an important new link between the RCAN1 gene and Huntington disease. Huntington disease is caused by expansion of glutamine repeats in the huntingtin protein. How the huntingtin protein with expanded polyglutamines (mutant huntingtin) causes the disease is still unclear, but phosphorylation of huntingtin appears to be protective. Increased huntingtin phosphorylation can be produced either by inhibition of the phosphatase calcineurin or by activation of the Akt kinase. The RCAN1 gene encodes regulators of calcineurin, and we now demonstrate, for the first time, that RCAN1-1L is depressed in Huntington disease. We also show that RCAN1-1L overexpression can protect against mutant huntingtin toxicity in an ST14A cell culture model of Huntington disease and that increased phos

SUBMITTER: Ermak G 

PROVIDER: S-EPMC2673253 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature