Blocking farnesylation of the prelamin A variant in Hutchinson-Gilford progeria syndrome alters the distribution of A-type lamins.

ABSTRACT: Mutations in the lamin A/C gene that cause Hutchinson-Gilford progeria syndrome lead to expression of a truncated, permanently farnesylated prelamin A variant called progerin. Blocking farnesylation leads to an improvement in the abnormal nuclear morphology observed in cells expressing progerin, which is associated with a re-localization of the variant protein from the nuclear envelope to the nuclear interior. We now show that a progerin construct that cannot be farnesylated is localized primarily in intranuclear foci and that its diffusional mobility is significantly greater than that of farnesylated progerin localized predominantly at the nuclear envelope. Expression of non-farnesylated progerin in transfected cells leads to a redistribution of lamin A and lamin C away from the nuclear e

SUBMITTER: Wang Y 

PROVIDER: S-EPMC3474666 | biostudies-literature | 2012 Sep-Oct

REPOSITORIES: biostudies-literature