ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders

Barrowman, Jemima; Michaelis, Susan

doi:10.1515/bc.2009.080

Cited by 52 publications

(68 citation statements)

References 86 publications

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“…Farnesylated-protein converting enzyme 1, also known as ZMPSTE24, is a membrane protease with seven predicted membrane spans (for a review see Barrowman and Michaelis, 2009;Liu and Zhou, 2008;Young et al, 2006). It performs a critical step in the processing of prelamin A in lamin A, a nuclear intermediate filament which provides nuclear structure and participates to heterochromatin organization and cell cycle control, removing the farnesyl tail of prelamin A (Mattout et al, 2006;Ramirez et al, 2007).…”

Section: M48 Familymentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Section: M48 Familymentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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“…"CAAX processing" comprises an ordered series of posttranslational biochemical reactions that result in prenylation of the cysteine residue of the CAAX motif, endoproteolysis of the AAX tripeptide, and carboxylmethylation of the prenylated cysteine. Historically, the a-factor precursor served as a valuable model for the discovery and functional analysis of the enzymes that mediate these CAAX-processing reactions (17,19,41,99,279).…”

Section: Introductionmentioning

confidence: 99%

Biogenesis of the Saccharomyces cerevisiae Pheromone a -Factor, from Yeast Mating to Human Disease

Michaelis¹,

Barrowman²

2012

Microbiol Mol Biol Rev

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101

106

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SUMMARY The mating pheromone a -factor secreted by Saccharomyces cerevisiae is a farnesylated and carboxylmethylated peptide and is unusually hydrophobic compared to other extracellular signaling molecules. Mature a -factor is derived from a precursor with a C-terminal CAAX motif that directs a series of posttranslational reactions, including prenylation, endoproteolysis, and carboxylmethylation. Historically, a -factor has served as a valuable model for the discovery and functional analysis of CAAX-processing enzymes. In this review, we discuss the three modules comprising the a -factor biogenesis pathway: (i) the C-terminal CAAX-processing steps carried out by Ram1/Ram2, Ste24 or Rce1, and Ste14; (ii) two sequential N-terminal cleavage steps, mediated by Ste24 and Axl1; and (iii) export by a nonclassical mechanism, mediated by the ATP binding cassette (ABC) transporter Ste6. The small size and hydrophobicity of a -factor present both challenges and advantages for biochemical analysis, as discussed here. The enzymes involved in a -factor biogenesis are conserved from yeasts to mammals. Notably, studies of the zinc metalloprotease Ste24 in S. cerevisiae led to the discovery of its mammalian homolog ZMPSTE24, which cleaves the prenylated C-terminal tail of the nuclear scaffold protein lamin A. Mutations that alter ZMPSTE24 processing of lamin A in humans cause the premature-aging disease progeria and related progeroid disorders. Intriguingly, recent evidence suggests that the entire a -factor pathway, including all three biogenesis modules, may be used to produce a prenylated, secreted signaling molecule involved in germ cell migration in Drosophila . Thus, additional prenylated signaling molecules resembling a -factor, with as-yet-unknown roles in metazoan biology, may await discovery.

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“…Its mammalian ortholog, farnesylated protein-converting enzyme 1 (FACE1 also known as Zmpste24), performs a critical cleavage that removes the hydrophobic farnesyl-modified tail of prelamin A (10). Knock-out mice show growth retardation, muscular dystrophy, and premature death; similarly, disruptive mutations in humans have drastic consequences for health and life span (11)(12)(13). HtpX, together with the ATP-dependent protein FtsH, participates in the quality control system of bacterial membrane proteins, which is essential for growth and survival of the cell (14 -17).…”

mentioning

confidence: 99%

A Novel Family of Soluble Minimal Scaffolds Provides Structural Insight into the Catalytic Domains of Integral Membrane Metallopeptidases

López-Pelegrín

Cerdà-Costa

Martínez-Jiménez

et al. 2013

Journal of Biological Chemistry

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Background: Structural characterization of integral-membrane (IM) metallopeptidases (MPs) faces enormous technical hurdles. Results:We have discovered a novel family of minimal MPs, minigluzincins, and determined the crystal structures of the zymogens of two family members. Conclusion:Minigluzincins are valid models for catalytic domains of M48 and M56 family IMMPs. Significance: They provide a high resolution scaffold for the design of small molecule inhibitors of IMMPs.

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ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders

Cited by 52 publications

References 86 publications

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Biogenesis of the Saccharomyces cerevisiae Pheromone a -Factor, from Yeast Mating to Human Disease

A Novel Family of Soluble Minimal Scaffolds Provides Structural Insight into the Catalytic Domains of Integral Membrane Metallopeptidases

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