ArticleHuman molecular genetics2012
Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 99 citations in OpenAlex.
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.The Journal of biological chemistry · 2026Article
- Prelamin A in anArteriosclerosis, thrombosis, and vascular biology · 2026Article
- Farnesylated prelamin A induces fibroblast polarity defects in premature aging disorders by inhibiting nesprin-2-SUN2 LINC complex function.Journal of cell science · 2026Article
- A manually curated gene-phenotype catalogue for progeroid syndromes and premature aging.Aging · 2026Article
- Stem cell-associated osteogenic deficiency causes craniofacial deformities with progeroid accumulation of prelamin A.JCI insight · 2026Article
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.bioRxiv : the preprint server for biology · 2026Article
- Restrictive Dermopathy in Neonates.Indian journal of pediatrics · 2026Article
- Attenuated Nuclear Tension Regulates Progerin-Induced Mechanosensitive Nuclear Wrinkling and Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Acyl-CoA-binding protein as a driver of pathological aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence.Journal of visualized experiments : JoVE · 2025Article
- TIPE2 gene transfer ameliorates aging-associated osteoarthritis in a progeria mouse model by reducing inflammation and cellular senescence.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Evaluating protein prenylation of human and viral CaaX sequences using a humanized yeast system.Disease models & mechanisms · 2024Article
- The farnesyl transferase inhibitor (FTI) lonafarnib improves nuclear morphology in ZMPSTE24-deficient fibroblasts from patients with the progeroid disorder MAD-B.Nucleus (Austin, Tex.) · 2023Article
- Prelamin A and ZMPSTE24 in premature and physiological aging.Nucleus (Austin, Tex.) · 2023Review
- A Humanized Yeast System for Evaluating the Protein Prenylation of a Wide Range of Human and Viral CaaX Sequences.bioRxiv : the preprint server for biology · 2023Article
- Can accelerated ageing models inform us on age-related tauopathies?Aging cell · 2023Review
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- Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular Pathology of Laminopathies.Annual review of pathology · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Likewise, mutations in the ZMPSTE24 gene that result in decreased enzyme function cause a spectrum of diseases that share certain features of premature aging. Twenty human ZMPSTE24 alleles have been identified that are associated with three disease categories of increasing severity: mandibuloacral dysplasia type B (MAD-B), severe progeria (atypical 'HGPS') and restrictive dermopathy (RD). To determine whether a correlation exists between decreasing ZMPSTE24 protease activity and increasing disease severity, we expressed mutant alleles of ZMPSTE24 in yeast and optimized in vivo yeast mating assays to directly compare the activity of alleles associated with each disease category. We also measured the activity of yeast crude membranes containing the ZMPSTE24 mutant proteins in vitro. We determined that, in general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with RD, whereas retention of partial, measureable activity results in MAD-B or severe progeria. Importantly, our assays can discriminate small differences in activity among the mutants, confirming that the methods presented here will be useful for characterizing any new ZMPSTE24 mutations that are discovered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.