Document Type
Article
Publication Date
2-21-1997
Description
The 72-kDa nuclear lamina protein lamin A is synthesized as a 74-kDa farnesylated precursor. Conversion of this precursor to mature lamin A appears to be mediated by a specific endoprotease. Prior studies of overexpressed wild-type and mutant lamin A proteins in cultured cells have indicated that the precursor possesses the typical carboxyl-terminal S- farnesylated, cysteine methyl ester and that farnesylation is required for endoproteolysis to occur. In this report, we describe the synthesis of an S- farnesyl, cysteinyl methyl ester peptide corresponding to the carboxyl- terminal 18 amino acid residues of human prelamin A. This peptide acts as a substrate for the prelamin A endoprotease in vitro, with cleavage of the synthetic peptide at the expected site between Tyr657 and Leu658. Endoproteolytic cleavage requires the S-prenylated cysteine methyl ester and, in agreement with transfection studies, is more active with the farnesylated than geranylgeranylated cysteinyl substrate. N-Acetyl farnesyl methyl cysteine is shown to be a noncompetitive inhibitor of the enzyme. Taken together, these observations suggest that there is a specific farnesyl binding site on the enzyme which is not at the active site.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Kilic, Fusun; Dalton, Marguerite B.; Burrell, Sarah K.; Mayer, John P.; Patterson, Scott D.; and Sinensky, Michael. 1997. In Vitro Assay and Characterization of the Farnesylation-Dependent Prelamin a Endoprotease. Journal of Biological Chemistry. Vol.272(8). 5298-5304. https://doi.org/10.1074/jbc.272.8.5298 PMID: 9030603 ISSN: 0021-9258
Copyright Statement
© 1997 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.