Research Perspective Volume 3, Issue 10 pp 943—954

Figure 1. Structure of prelamin A, lamin A and progerin. Lamin A is synthesized as a 74-kDa precursor, prelamin A. The C-terminal CaaX motif of prelamin A undergoes a series of posttranslational modifications including CaaX processing (farnesylation, aaX cleavage and carboxylmethylation), followed by endoproteolytic cleavage by Zmpste24. Zmpste24 is responsible for the sequential proteolytic cleavage and processing of prelamin A into mature lamin A (70-kDa). The point mutation identified from HGPS patients, results in the activation of an aberrant cryptic splice site causing the deletion of a 50 amino acid region from the C-terminal end of prelamin A. Hence, prelamin A cannot undergo complete processing into mature lamin A in HGPS patients, and a truncated protein called as progerin accumulates in cells.