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 envelope into intranuclear foci but does not significantly 
affect the localization of endogenous lamin B1 at nuclear envelope. There is a 
similar redistribution of lamin A and lamin C into intranuclear foci in 
transfected cells expressing progerin in which protein farnesylation is blocked 
by treatment with a protein farnesyltransferase inhibitor. Blocking 
farnesylation of progerin can lead to a redistribution of normal A-type lamins 
away from the inner nuclear envelope. This may have implications for using drugs 
that block protein prenylation to treat children with Hutchinson-Gilford 
progeria syndrome. These findings also provide additional evidence that A-type 
and B-type lamins can form separate microdomains within the nucleus.