No

The discovery of mammalian protein prenylation was originally motivated by an effort to identify a nonsterol isoprenoid which indirect evidence suggested was a coregulator of isoprenoid biosynthesis and played a critical role in cellular proliferation. The first prenylated proteins to be identified were the nuclear lamin proteins-B lamins and prelamin A-which were subsequently shown to be farnesylated at a carboxyl-terminal CAAX motif. In both types of lamin, the farnesylation and carboxymethylation play a role in targeting these proteins to the nuclear envelope. The nucleus can be demonstrated to be a CAAX processing compartment for the lamins. In the case of prelamin A, there is removal of a carboxyl-terminal polypeptide which is specifically catalyzed by the enzyme Zmpste24. This processing event is necessary for assembly of lamin A into the lamina and may play a role in cell cycle control. Because the nucleus contains only one target membrane, lamin farnesylation and carboxymethylation may be sufficient to allow association with this membrane. This stands in contrast to farnesylated proteins expressed in the cytoplasm.

The maturation of lamin A is completed by the endoproteolytic cleavage of its farnesylated precursor protein, prelamin A. In the absence of this cleavage, prelamin A can neither give rise to lamin A nor assemble into the nuclear lamina. We call the enzyme which catalyzes this endoproteolytic step the 'prelamin A endoprotease'. In this study, we begin characterization of the regulation of prelamin A endoprotease. In particular, we address the question as to whether prelamin A endoprotease activity is constitutive in cells or responds to expression of prelamin A. To do this, we compared the activity of this novel endoprotease in cells which express prelamin A with those that do not. Our data shows that the enzymatic activity of prelamin A endoprotease is enhanced by the expression of prelamin A.