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zinc metallopeptidase (STE24 homolog, S. cerevisiae)
Other data
EC number3.4.24.84
LocusChr. 1 p34

ZMPSTE24 is a human gene.[1][2] The protein encoded by this gene is a metallopeptidase. It is involved in the processing of lamin A.[3] Defects in the ZMPSTE24 gene lead to similar laminopathies as defects in lamin A, because the latter is a substrate for the former.[4] In humans, a mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder.[5] Failure to correctly process prelamin A leads to deficient ability to repair DNA double-strand breaks.[6][7]

As shown by Liu et al.,[8] lack of Zmpste24 prevents lamin A formation from its precursor farnesyl-prelamin A. Lack of Zmpste24 causes progeroid phenotypes in mice and humans. This lack increases DNA damage and chromosome aberrations and sensitivity to DNA-damaging agents that cause double-strand breaks. Also, lack of Zmpste24 allows an increase in non-homologous end joining, but a deficiency in steps leading to homologous recombinational DNA repair.

See also


  1. Tam A, Nouvet FJ, Fujimura-Kamada K, Slunt H, Sisodia SS, Michaelis S (August 1998). "Dual roles for Ste24p in yeast a-factor maturation: NH2-terminal proteolysis and COOH-terminal CAAX processing". J. Cell Biol. 142 (3): 635–49. doi:10.1083/jcb.142.3.635. PMC 2148179. PMID 9700155.
  2. Freije JM, Blay P, Pendás AM, Cadiñanos J, Crespo P, López-Otín C (June 1999). "Identification and chromosomal location of two human genes encoding enzymes potentially involved in proteolytic maturation of farnesylated proteins". Genomics. 58 (3): 270–80. doi:10.1006/geno.1999.5834. PMID 10373325.
  3. Young SG, Fong LG, Michaelis S (December 2005). "Prelamin A, Zmpste24, misshapen cell nuclei, and progeria--new evidence suggesting that protein farnesylation could be important for disease pathogenesis". J. Lipid Res. 46 (12): 2531–58. doi:10.1194/jlr.R500011-JLR200. PMID 16207929.
  4. Varela I, Cadiñanos J, Pendás AM, Gutiérrez-Fernández A, Folgueras AR, Sánchez LM, Zhou Z, Rodríguez FJ, Stewart CL, Vega JA, Tryggvason K, Freije JM, López-Otín C (September 2005). "Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation". Nature. 437 (7058): 564–8. doi:10.1038/nature04019. PMID 16079796.
  5. Wang Y, Lichter-Konecki U, Anyane-Yeboa K, Shaw JE, Lu JT, Östlund C, Shin JY, Clark LN, Gundersen GG, Nagy PL, Worman HJ (2016). "A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder". J. Cell Sci. 129 (10): 1975–80. doi:10.1242/jcs.187302. PMC 4878994. PMID 27034136.
  6. Redwood AB, Perkins SM, Vanderwaal RP, Feng Z, Biehl KJ, Gonzalez-Suarez I, Morgado-Palacin L, Shi W, Sage J, Roti-Roti JL, Stewart CL, Zhang J, Gonzalo S (2011). "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549–60. doi:10.4161/cc.10.15.16531. PMC 3180193. PMID 21701264.
  7. Gonzalo S, Kreienkamp R (2015). "DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome". Curr. Opin. Cell Biol. 34: 75–83. doi:10.1016/ PMC 4522337. PMID 26079711.
  8. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadiñanos J, López-Otín C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z (2005). "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780–5. doi:10.1038/nm1266. PMID 15980864.

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