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Description

Prelamin-A/C (UniProt: P48678) is encoded by the Lmna (also known as Lmn1) gene (Gene ID: 16905) in murine species. Lamins are components of the nuclear lamina that provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. They play an important role in nuclear assembly, chromatin organization, nuclear membrane, and telomere dynamics. Unlike mature lamin A, prelamin A accumulates as discrete and localized foci at the nuclear periphery. Prelamin-A/C is synthesized with two pro-peptides (aa 648-662 and 663-665) that are subsequently cleaved off to produce Lamin A/C (aa 1-647). The prelamin-A/C maturation pathway includes farnesylation of CAAX motif, ZMPSTE24 mediated cleavage of the last three amino acids, methylation of the C-terminal cysteine and endoproteolytic removal of the last 15 C-terminal amino acids. ZMPSTE24 is shown to be essential for the conversion of farnesyl-prelamin A to mature lamin . In the absence of ZMPSTE24 farnesyl-prelamin A accumulates in the nucleus and results in toxicity causing a variety of disease phenotypes. Failure to convert prelamin A to lamin A has been linked to cardiac myopathy. Prelamin A/C can accelerate smooth muscle cell senescence. It can act to disrupt mitosis and induce DNA damage in vascular smooth muscle cells, leading to mitotic failure, genomic instability, and premature senescence. Mutations in Lmna gene is known to cause skeletal and cardiac myopathies, sarcopenia, osteopenia, decreased bone formation, and decreased muscle growth. (Ref.: Heizer, PJ., et al. (2020). J. Lipid Res. 61, 413-421, Li, W., et al. (2011). PLoS One. 6(4), e19313, Davies, BSJ., et al. (2010). Human Mol. Gen. 19(13), 2682-2694).