title: Investigating the purpose of prelamin A processing.
abstract: Lmna yields two major protein products in somatic cells, lamin C and prelamin A. Mature lamin A is produced from prelamin A by four posttranslational processing steps-farnesylation of a carboxyl-terminal cysteine, release of the last three amino acids of the protein, methylation of the farnesylcysteine, and the endoproteolytic release of the carboxyl-terminal 15 amino acids of the protein (including the farnesylcysteine methyl ester). Although the posttranslational processing of prelamin A has been conserved in vertebrate evolution, its physiologic significance remains unclear. Here we review recent studies in which we investigated prelamin A processing with Lmna knock-in mice that produce exclusively prelamin A (Lmna(PLAO)), mature lamin A (Lmna(LAO)) or nonfarnesylated prelamin A (Lmna(nPLAO)). We found that the synthesis of lamin C is dispensable in laboratory mice, that the direct production of mature lamin A (completely bypassing all prelamin A processing) causes no discernable pathology in mice, and that exclusive production of nonfarnesylated prelamin A leads to cardiomyopathy.
authors.affiliation: Department of Medicine, University of California, Los Angeles, USA.
authors.forename: Brandon Sj
authors.initials: BS
authors.lastname: Davies
authors.forename: Catherine
authors.initials: C
authors.lastname: Coffinier
authors.forename: Shao H
authors.initials: SH
authors.lastname: Yang
authors.forename: Richard H
authors.initials: RH
authors.lastname: Barnes
authors.forename: Hea-Jin
authors.initials: HJ
authors.lastname: Jung
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
mesh_terms: D000818:Animals; D034904:Lamin Type A; D034882:Lamins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011371:Progeria / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism*; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational
chemical_list: D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A