Format

Send to

Choose Destination
Exp Cell Res. 2012 Jan 1;318(1):1-7. doi: 10.1016/j.yexcr.2011.08.009. Epub 2011 Aug 16.

Lamin A, farnesylation and aging.

Author information

1
Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Abstract

Lamin A is a component of the nuclear envelope that is synthesized as a precursor prelamin A molecule and then processed into mature lamin A through sequential steps of posttranslational modifications and proteolytic cleavages. Remarkably, over 400 distinct point mutations have been so far identified throughout the LMNA gene, which result in the development of at least ten distinct human disorders, collectively known as laminopathies, among which is the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin. The mechanism by which progerin leads to premature aging and the classical HGPS disease phenotype as well as the relationship between this disorder and the onset of analogous symptoms during the lifespan of a normal individual are not well understood. Yet, recent studies have provided critical insights on the cellular processes that are affected by accumulation of progerin and have suggested that cellular alterations in the lamin A processing pathway leading to the accumulation of farnesylated prelamin A intermediates may play a role in the aging process in the general population. In this review we provide a short background on lamin A and its maturation pathway and discuss the current knowledge of how progerin or alterations in the prelamin A processing pathway are thought to influence cell function and contribute to human aging.

PMID:
21871450
PMCID:
PMC4209918
DOI:
10.1016/j.yexcr.2011.08.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center