Gene Symbol: Zmpste24
Description: zinc metallopeptidase, STE24
Alias: A530043O15Rik, D030046F19, FACE1, Face-1, MADB, STE24, Ste24p, CAAX prenyl protease 1 homolog, farnesylated-proteins converting enzyme 1, prenyl protein-specific endoprotease 1, zinc metallopeptidase, STE24 homolog, zinc metalloproteinase, STE24 homolog
Species: mouse
Products:     Zmpste24

Top Publications

  1. Zhang H, Kieckhaefer J, Cao K. Mouse models of laminopathies. Aging Cell. 2013;12:2-10 pubmed publisher
    ..This review groups these LMNA-related mouse models into three categories: null mutants, point mutants, and progeroid mutants. We compare their phenotypes and discuss their potential implications in laminopathies and aging. ..
  2. Pendas A, Zhou Z, Cadinanos J, Freije J, Wang J, Hultenby K, et al. Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat Genet. 2002;31:94-9 pubmed
    The mouse ortholog of human FACE-1, Zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones...
  3. Coffinier C, Jung H, Li Z, Nobumori C, Yun U, Farber E, et al. Direct synthesis of lamin A, bypassing prelamin a processing, causes misshapen nuclei in fibroblasts but no detectable pathology in mice. J Biol Chem. 2010;285:20818-26 pubmed publisher
    ..The last cleavage step, mediated by ZMPSTE24, releases mature lamin A...
  4. Varela I, Pereira S, Ugalde A, Navarro C, Suarez M, Cau P, et al. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med. 2008;14:767-72 pubmed publisher
    ..and prelamin A and markedly improves the aging-like phenotypes of mice deficient in the metalloproteinase Zmpste24, including growth retardation, loss of weight, lipodystrophy, hair loss and bone defects...
  5. Fong L, Frost D, Meta M, Qiao X, Yang S, Coffinier C, et al. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 2006;311:1621-3 pubmed
    ..We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria...
  6. Varela I, Cadinanos J, Pendas A, Gutierrez Fernandez A, Folgueras A, Sanchez L, et al. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature. 2005;437:564-8 pubmed
    b>Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A (Lmna), an essential component of the nuclear envelope...
  7. Fong L, Ng J, Meta M, Coté N, Yang S, Stewart C, et al. Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc Natl Acad Sci U S A. 2004;101:18111-6 pubmed
    b>Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina...
  8. Liu B, Wang J, Chan K, Tjia W, Deng W, Guan X, et al. Genomic instability in laminopathy-based premature aging. Nat Med. 2005;11:780-5 pubmed
    ..Lack of functional Zmpste24, a metalloproteinase responsible for the maturation of prelamin A, also results in progeroid phenotypes in mice ..
  9. Soria Valles C, Osorio F, Gutiérrez Fernández A, De Los Angeles A, Bueno C, Menéndez P, et al. NF-κB activation impairs somatic cell reprogramming in ageing. Nat Cell Biol. 2015;17:1004-13 pubmed publisher

More Information


  1. Davies B, Barnes R, Tu Y, Ren S, Andres D, Spielmann H, et al. An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum Mol Genet. 2010;19:2682-94 pubmed publisher
    ..The latter finding is potentially relevant to the long-term use of protein farnesyltransferase inhibitors, which lead to an accumulation of non-farnesylated prelamin A. ..
  2. Mariño G, Ugalde A, Salvador Montoliu N, Varela I, Quirós P, Cadinanos J, et al. Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum Mol Genet. 2008;17:2196-211 pubmed publisher
    ..In this work, we describe the unexpected finding that Zmpste24-null mice, which show accelerated aging and are a reliable model of human Hutchinson-Gilford progeria, exhibit an ..
  3. Fu B, Wang L, Li S, Dorf M. ZMPSTE24 defends against influenza and other pathogenic viruses. J Exp Med. 2017;214:919-929 pubmed publisher
    Zinc metallopeptidase STE24 (ZMPSTE24) is a transmembrane metalloprotease whose catalytic activity is critical for processing lamin A on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum...
  4. Rivera Torres J, Calvo C, Llach A, Guzmán Martínez G, Caballero R, González Gómez C, et al. Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations. Proc Natl Acad Sci U S A. 2016;113:E7250-E7259 pubmed
    ..We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24-/- mouse model of HGPS...
  5. Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun. 2013;4:1868 pubmed publisher
    ..Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson-Gilford progeria syndrome...
  6. Bergo M, Gavino B, Ross J, Schmidt W, Hong C, Kendall L, et al. Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc Natl Acad Sci U S A. 2002;99:13049-54 pubmed
    b>Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum...
  7. Coffinier C, Hudon S, Farber E, Chang S, Hrycyna C, Young S, et al. HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc Natl Acad Sci U S A. 2007;104:13432-7 pubmed
    ..rapidly than nonfarnesylated prelamin A, comigrating with the farnesylated form of prelamin A that accumulates in ZMPSTE24-deficient fibroblasts...
  8. Leung G, Schmidt W, Bergo M, Gavino B, Wong D, Tam A, et al. Biochemical studies of Zmpste24-deficient mice. J Biol Chem. 2001;276:29051-8 pubmed
    ..In this study, we cloned mouse Zmpste24, the orthologue for yeast STE24 and showed that it could promote a-factor production when expressed in yeast...
  9. Krishnan V, Chow M, Wang Z, Zhang L, Liu B, Liu X, et al. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci U S A. 2011;108:12325-30 pubmed publisher
    ..Gilford progeria syndrome is largely recapitulated in mice deficient for the lamin A-processing enzyme, Zmpste24. We have previously reported that Zmpste24 deficiency results in genomic instability and early cellular ..
  10. Fong L, Ng J, Lammerding J, Vickers T, Meta M, Coté N, et al. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest. 2006;116:743-52 pubmed accumulation of farnesyl-prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes...
  11. Liu M, Sjogren A, Karlsson C, Ibrahim M, Andersson K, Olofsson F, et al. Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer. Proc Natl Acad Sci U S A. 2010;107:6471-6 pubmed publisher
    ..These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics. ..
  12. Ibrahim M, Sayin V, Akula M, Liu M, Fong L, Young S, et al. Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria. Science. 2013;340:1330-3 pubmed publisher
    Several progeroid disorders, including Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (ZMPSTE24 deficiency), arise when a farnesylated and methylated form of prelamin A accumulates at the nuclear envelope...
  13. Lee R, Chang S, Trinh H, Tu Y, White A, Davies B, et al. Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes. Hum Mol Genet. 2010;19:1603-17 pubmed publisher
    ..Like Fntb-deficient keratinocytes, Pggt1b-deficient keratinocytes did not proliferate in culture. Thus, both FTase and GGTase-I are required for the homeostasis of skin keratinocytes. ..
  14. Mariño G, Ugalde A, Fernández A, Osorio F, Fueyo A, Freije J, et al. Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function. Proc Natl Acad Sci U S A. 2010;107:16268-73 pubmed publisher
    b>Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A, an essential component of the nuclear envelope...
  15. Agarwal A, Zhou X, Hall R, Nicholls K, Bankier A, Van Esch H, et al. Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. J Investig Med. 2006;54:208-13 pubmed publisher
    ..are known for MAD: lamin A/C (LMNA), encoding structural nuclear lamina proteins, and zinc metalloproteinase (ZMPSTE24), a membrane-bound endoprotease involved in post-translational proteolytic cleavage of carboxy terminal residues ..
  16. Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, et al. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 2012;16:738-50 pubmed publisher
    ..activity in the presence of progerin or prelamin A, leading to rapid depletion of adult stem cells (ASCs) in Zmpste24(-/-) mice. Resveratrol enhances the binding between SIRT1 and A-type lamins to increases its deacetylase activity...
  17. Osorio F, Varela I, Lara E, Puente X, Espada J, Santoro R, et al. Nuclear envelope alterations generate an aging-like epigenetic pattern in mice deficient in Zmpste24 metalloprotease. Aging Cell. 2010;9:947-57 pubmed publisher
    Mutations in the nuclear envelope protein lamin A or in its processing protease ZMPSTE24 cause human accelerated aging syndromes, including Hutchinson-Gilford progeria syndrome...
  18. Imai R, Asai K, Hanai J, Takenaka M. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation. Aging (Albany NY). 2015;7:486-99 pubmed
    ..we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice...
  19. Osorio F, Bárcena C, Soria Valles C, Ramsay A, de Carlos F, Cobo J, et al. Nuclear lamina defects cause ATM-dependent NF-?B activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 2012;26:2311-24 pubmed publisher
    ..and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice)...
  20. Chang S, Hudon Miller S, Yang S, Jung H, Lee J, Farber E, et al. Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation in cells by inhibiting ZMPSTE24. J Lipid Res. 2012;53:1176-82 pubmed publisher
    ..hypothesis-GGTIs are not specific for GGTase-I, and they lead to prelamin A accumulation by inhibiting ZMPSTE24 (a zinc metalloprotease that converts farnesyl-prelamin A to mature lamin A)...
  21. Yang S, Procaccia S, Jung H, Nobumori C, Tatar A, Tu Y, et al. Mice that express farnesylated versions of prelamin A in neurons develop achalasia. Hum Mol Genet. 2015;24:2826-40 pubmed publisher
    ..achalasia, was observed in genetically modified mice that express full-length farnesyl-prelamin A in neurons (Zmpste24-deficient mice carrying two copies of a Lmna knock-in allele yielding full-length prelamin A transcripts lacking ..
  22. Ugalde A, Ramsay A, de la Rosa J, Varela I, Mariño G, Cadinanos J, et al. Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53. EMBO J. 2011;30:2219-32 pubmed publisher
    ..To address this question, we have analysed miRNA levels in Zmpste24-deficient mice, a model of Hutchinson-Gilford progeria syndrome...
  23. Jung H, Coffinier C, Choe Y, Beigneux A, Davies B, Yang S, et al. Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proc Natl Acad Sci U S A. 2012;109:E423-31 pubmed publisher
    ..The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology. ..
  24. Coffinier C, Hudon S, Lee R, Farber E, Nobumori C, Miner J, et al. A potent HIV protease inhibitor, darunavir, does not inhibit ZMPSTE24 or lead to an accumulation of farnesyl-prelamin A in cells. J Biol Chem. 2008;283:9797-804 pubmed publisher
    ..We recently demonstrated that a commonly used HIV-PI, lopinavir, inhibits ZMPSTE24, thereby blocking lamin A biogenesis and leading to an accumulation of prelamin A...
  25. Zeng F, Schultz R. Gene expression in mouse oocytes and preimplantation embryos: use of suppression subtractive hybridization to identify oocyte- and embryo-specific genes. Biol Reprod. 2003;68:31-9 pubmed
    ..Further characterization of the subtracted oocyte and 8-cell embryo cDNA libraries should furnish a trove of information regarding temporal changes in gene expression during oogenesis and preimplantation development in the mouse. ..
  26. Li S, Fu B, Wang L, Dorf M. ZMPSTE24 Is Downstream Effector of Interferon-Induced Transmembrane Antiviral Activity. DNA Cell Biol. 2017;36:513-517 pubmed publisher
    The zinc metalloprotease ZMPSTE24 is a constitutively and ubiquitously expressed host restriction factor that is responsible for limiting infection by a broad spectrum of enveloped viruses, including influenza A, vesicular stomatitis, ..