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Nucleus. 2011 Jan-Feb;2(1):4-9. doi: 10.1093/hmg/ddq158.

Investigating the purpose of prelamin A processing.

Author information

1
Department of Medicine, University of California, Los Angeles, USA.

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.

KEYWORDS:

cardiomyopathy; prelamin A; progeria; protein farnesylation; restrictive dermopathy

PMID:
21647293
PMCID:
PMC3104803
DOI:
10.4161/nucl.2.1.13723
[Indexed for MEDLINE]
Free PMC Article
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