Fig. 3.

Block in the CaaX processing of progerin by mutation of the CaaX motif (C→S) and pharmacological (FTI) treatment. (A) Normally, progerin is expected to undergo C-terminal CaaX processing (steps 1-3) but no Zmpste24-mediated internal processing (step 4), resulting in persistent CaaX modifications. (B) A mutational block at step 1 in CaaX processing by introduction of a C→S mutation prevents the farnesylation and subsequent processing of progerin. (C) Pharmacological treatment with an FTI will likewise prevent farnesylation of progerin at step 1 and, thus, its subsequent processing.