ZMPSTE24 Mutations, Lamin A Processing & Laminopathies

ZMPSTE24 (FACE-1, CAAX prenyl protease 1 homolog) is a membrane associated zinc metalloprotease of the peptidase M48A family. It's catalytic activity can be defined as the peptide bond hydrolyzed in the sequence -C-|-A-A-X in which C is an S-isoprenylated cysteine residue, A is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids. It has been shown to specifically cleave the final 3 carboxy terminal residues from farnesylated prelamin A to form mature lamin A.

Mutations in ZMPSTE24 have been linked to a rare disorder known as Restrictive dermopathy (Lethal Tight Skin Contracture Syndrome).  This syndrome is characterized by intrauterine growth retardation, thin, tightly adherent translucent skin, superficial vessels, typical facial dysmorphism as well as generalized joint contractures. In a sibling study it was shown that 2 frameshift mutations that were inherited in an autosomally recessive manner were responsible for the syndrome manifestation (PMID: 20101687).

ZMPSTE24 mutations, as well as abnormal processing of Lamin A are also associated with laminopathies.  ZMPSTE24 (-/-) mice show lipodystrophy, accumulation of Lamin A and altered processing of the cytoskeleton protein, vimentin.  Protein networks related to mitochondrial function, including those involved in tricarboxylic acid cycle and oxidative phosphorylation, were up-regulated in ZMPSTE24 (-/-) mice.  All of these symptoms are characteristic of progeria which causes premature aging in mice and humans. (PMID: 218282)  Continued study of ZMPSTE24 mutations and their affects may lead to new understanding and therapeutic approaches to treating laminopathies.

Novus offers 3 ZMPSTE24 antibodies (NB100-2387, NB100-2388 and NB100-53794) in various conjugation formats, for your research needs. Please contact our technical support department (technical@novusbio.com) with any questions.