Document Type

Article

Publication Date

1-1-2006

Publication Title

Journal of Cell Science

Volume

119

First Page

3265

Last Page

3272

DOI

10.1242/​jcs.03156

Keywords

progeroid, transferase, inhibitors

Disciplines

Biochemistry | Molecular Biology | Other Chemistry

Abstract

Three mammalian nuclear lamin proteins, lamin B1, lamin B2 and the lamin A precursor, prelamin A, undergo canonical farnesylation and processing at CAAX motifs. In the case of prelamin A, there is an additional farnesylation-dependent endoproteolysis, which is defective in two congenital diseases: Hutchinson-Gilford progeria (HGPS) and restrictive dermopathy (RD). These two diseases arise respectively from defects in the prelamin A substrate and the enzyme (ZmpSte24) that processes it. Recent work has shed light on the roles of the lamin proteins and the enzymes involved in their farnesylation-dependent maturation. Other experimental work, including mouse model studies, have examined the possibility that farnesyl transferase inhibitors can represent effective treatment for HGPS. However, there are concerns about their use for this purpose given the potential for alternative prenylation pathways.

Comments

Copyright © 2006 The Company of Biologists. The published article may be found online at: http://jcs.biologists.org/content/119/16/3265.abstract.

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