Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
Three mammalian nuclear lamin proteins, lamin B(1), lamin B(2) 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.
Rusiñol
Antonio E
AE
Department of Biochemistry and Molecular Biology, Box 70581, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37164-0581, USA.
Sinensky
Michael S
MS
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011371:Progeria / Q000201:enzymology / Q000628:therapy; D017368:Protein Prenylation; D012868:Skin Abnormalities / Q000201:enzymology / Q000628:therapy; D013577:Syndrome
D004791:Enzyme Inhibitors; D034882:Lamins; D008074:Lipoproteins; D008565:Membrane Proteins; D051231:Farnesyltranstransferase; D045726:Metalloproteases; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse; C120130:ZMPSTE24 protein, human