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Investigating the purpose of prelamin A processing
Journal article   Open access

Investigating the purpose of prelamin A processing

Brandon SJ Davies, Catherine Coffinier, Shao H Yang, Richard H Barnes, Hea-Jin Jung, Stephen G Young and Loren G Fong
Nucleus (Austin, Tex.), Vol.2(1), pp.4-9
01/01/2011
DOI: 10.4161/nucl.2.1.13723
PMCID: PMC3104803
PMID: 21647293
url
https://europepmc.org/articles/pmc3104803View
Published (Version of record) Open Access

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.
cardiomyopathy Extra View prelamin A progeria protein farnesylation restrictive dermopathy

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