zinc metallopeptidase (STE24 homolog, S. cerevisiae)
Identifiers
SymbolZMPSTE24
NCBI gene10269
HGNC12877
OMIM606480
RefSeqNM_005857
UniProtO75844
Other data
EC number3.4.24.84
LocusChr. 1 p34
Search for
StructuresSwiss-model
DomainsInterPro

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

References

  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. Bibcode:2005Natur.437..564V. doi:10.1038/nature04019. PMID 16079796. S2CID 4394115.
  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/j.ceb.2015.05.007. 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. S2CID 11798376.



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