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Editorial
. 2018 Jul 17;138(3):283-286.
doi: 10.1161/CIRCULATIONAHA.118.034480.

Permanently Farnesylated Prelamin A, Progeria, and Atherosclerosis

Howard J Worman  1 , Susan Michaelis  2
Affiliations
Editorial

Permanently Farnesylated Prelamin A, Progeria, and Atherosclerosis

Howard J Worman et al. Circulation. .
No abstract available

Keywords: Editorials; atherosclerosis; lamin; progeria.

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Figures

Figure 1
Figure 1
Prelamin A processing and diseases caused by mutations in genes altering it. A, Prelamin A processing pathway. In Step 1, protein farnesyltransferase (FTase) catalyzes the addition of a farnesyl lipid moiety to the cysteine residue of the CAAX motif (CSIM in prelamin A). In Step 2, the terminal three amino acids (SIM) are cleaved in a reaction catalyzed by zinc metalloproteinase STE24 (ZMPSTE24) or Ras converting CAAX endopeptidase 1 (RCE1) (Figure 1A, step 2). In Step 3, isoprenylcysteine carboxyl methyltransferase (ICMT) catalyzes the carboxymethylation of the farnesylcysteine. In Step 4, ZMPSTE24 recognizes the farnesylated protein and catalyzes the cleavage of the last 15 amino acids of prelamin A, including its farnesylated cysteine, resulting in the production of mature, unfarnesylated lamin A. B, Defective prelamin A processing results in expression of permanently farnesylated forms of prelamin A and progeroid diseases. Recessive mutations in ZMPSTE24 cause RD and MAD (top); a dominant mutation LMNA L647R disrupts prelamin A cleavage causing a progeroid disorder (middle); dominant G608G (or rarely G608S) mutations in LMNA generate a prelamin A variant with an internal deletion of 50 amino acids and cause HGPS; the truncated prelamin A variant is called progerin.
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Comment on

References

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