Ask about this productRelated genes to: ZMPSTE24 antibody
- Gene:
- ZMPSTE24 NIH gene
- Name:
- zinc metallopeptidase STE24
- Previous symbol:
- -
- Synonyms:
- FACE-1, Ste24p, STE24, HGPS, PRO1
- Chromosome:
- 1p34.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-17
- Date modifiied:
- 2019-04-23
Related products to: ZMPSTE24 antibody
Related articles to: ZMPSTE24 antibody
- Disrupted processing of prelamin A (encoded by LMNA) causes Hutchinson-Gilford progeria syndrome (HGPS) and related premature aging disorders. The farnesylated prelamin A variant produced in HGPS, termed progerin, alters actin-nuclear interactions mediated by nesprin-2 and SUN2 linker of nucleoskeleton and cytoskeleton (LINC) complexes, resulting in defective cell polarization. To explore further how prelamin A causes these cellular defects, we examined other disease-causing variants that prevent cleavage of lamin A or reduce the activity of the processing enzyme ZMPSTE24. Accumulation of prelamin A or an uncleaved variant in cells reduced diffusional mobilities of nesprin-2 and SUN2 and inhibited their function in cell polarization in a farnesylation-dependent manner. Expression of short carboxyl-terminal tail fragments of prelamin A variants disrupted cell polarity in a farnesylation-dependent fashion. These results show that retention of the farnesyl moiety in the tails of prelamin A or its variants is the common element responsible for disrupting actin force transmission to the nucleus in premature aging syndromes and support the idea that altered function of actin-dependent LINC complexes is a critical component of premature aging. - Source: PubMed
Publication date: 2026/05/18
Lio ChonkitWang YuexiaWilson Paige CLi YutaoAntoku SusumuÖstlund CeciliaShin Ji-YeonWorman Howard JChang WakamGundersen Gregg G - An estimated 189 million bone fractures occurred in 2019 making it one of the most globally prevalent injuries. Delayed union or nonunion occurs in up to 15% of normal fractures with higher rates in aged individuals. Preclinical testing supports the translation of novel strategies to promote improved fracture repair, but there is a paucity of small animal models that recapitulate delayed fracture healing. Here, we evaluated the Zmpste24 (Z24 ) murine model of Hutchinson-Gilford progeria syndrome as a model of delayed fracture healing. Leveraging the previously characterized Z24 phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that progeria mice will present with significantly delayed fracture healing relative to age-matched wild type (WT) controls. Mice received intramedullary-fixed tibia fractures with healing and immunosenescence evaluated throughout repair. Z24 mice demonstrated significantly delayed healing with smaller fracture calli containing more cartilage and less bone relative to WT mice. The fracture healing phenotype of the Z24 phenocopied naturally aged mice with increased systemic senescence noted in animals relative to adult WT. Unlike naturally aged mice, Z24 also presented with frail bones. Z24 showed a dysregulated immune composition, with decreased lymphopoiesis, increased myelopoiesis and neutrophil accumulation. Aspects of the macrophage phenotype in Z24 reflected changes in natural aging, but with different systemic T cell responses. Given the Z24 progeria mouse model demonstrates the delayed fracture healing phenotype of naturally aged animal at 3 rather than 20 months of age, we suggest this model provides an accelerated model of age-related delayed fracture healing. - Source: PubMed
Duke Victoria RPhilippon Marc JLind Dane R GKasler HerbertYamaura KoheiHuard MattCzachor MollyHollenbeck JustinBrown JustinGarcia AlexMatityahu Jacob DFukase NaomasaMarcucio Ralph SNelson Anna-LauraHambright William SSnapper Dustin MHuard JohnnyBahney Chelsea S - Restrictive Dermopathy (RD, OMIM #275210) is an ultra-rare, lethal genodermatosis caused by defects in lamins and related proteins. RD is caused by biallelic pathogenic variants in ZMPSTE24, which encodes zinc metallopeptidase ZMPSTE24, an enzyme essential for processing prelamin A, the precursor of lamin A. While null variants leading to a total loss of prelamin A processing have been related to neonatally lethal RD, variants preserving residual prelamin A processing function cause an allelic disorder called Mandibuloacral Dysplasia Type B (MAD-B). RD is characterized by taut translucent skin, visible superficial vessels, joint contractures, and dysmorphic features, with death usually occurring within the first month of life. Cardiac anomalies, including ASD and PDA, have been reported in a few patients, most of whom were not genetically confirmed, and transposition of the great arteries (TGA) has been described only once, also without molecular confirmation. We report a patient with restrictive dermatopathy (RD) presenting with double outlet right ventricle (DORV) and pulmonary valve atresia which have not been previously reported in association with RD. Exome Sequencing (ES) was performed, revealing a novel homozygous splice-site variant in ZMPSTE24 (c.1203 + 1G>T). Segregation analysis was performed in the mother and two siblings. To our knowledge, DORV has not previously been reported in an RD patient. This case expands the genotypic spectrum of RD and suggests a possible link with complex cardiac malformations. - Source: PubMed
Publication date: 2026/03/25
Kındış ErdemVarol Ömer - The biogenesis of integral membrane proteins is complex, as revealed by an ever-growing number of cellular components shown to be dedicated to the insertion, folding, surveillance, rectification, or quality control of specific client membrane proteins. The zinc metalloprotease ZMPSTE24 and its yeast homolog Ste24 have well-established roles in the proteolytic maturation of the nuclear scaffold protein lamin A and yeast a-factor, respectively. Additionally, Ste24 has been implicated through yeast genetic screens in a variety of membrane processes, including ER- associated degradation (ERAD), Sec61 translocon "unclogging," the unfolded protein response (UPR), and potentially as a membrane protein topology determinant. Recently, an interaction was demonstrated between ZMPSTE24 and the antiviral interferon induced transmembrane protein IFITM3, although the functional significance of this interaction is not well-understood. IFITM3 is a tail-anchored protein with a cytoplasmic N-terminus, a single transmembrane span, and a lumenal/exocellular C-terminus. Here, we show that a catalytic-dead version of ZMPSTE24, ZMPSTE24, exhibits enhanced binding to IFITM3, and this bound species of IFITM3 is hypo-palmitoylated. Using a split fluorescence topology reporter, we demonstrate that ZMPSTE24 "traps" and stabilizes a subpopulation of IFITM3 molecules with an atypical membrane topology, whose C-terminus is cytosolic instead of lumenal. Such inverted forms of IFITM3 are also detected in the presence of ERAD inhibitors when ZMPSTE24 is absent. We hypothesize the ZMPSTE24 trap mutant reveals a normally transient isoform of IFITM3 whose transmembrane span is inverted and that ZMPSTE24 is involved in the quality control of IFITM3 topology, either inverting, correcting or assisting in removal of aberrant IFITM3 molecules. - Source: PubMed
Publication date: 2026/03/02
Spear Eric DShilagardi KhurtsSarju SoniaMichaelis Susan - Interventional therapy and surgery play important roles in the treatment of various diseases, but they cause varying degrees of vascular injury. Currently, the side effects are often overlooked. Here, we observed abnormal nuclear morphology (nuclear dysmorphism) and vascular aging in injured human and rodent arteries. Platelet-derived microvesicles (PMVs) adhere to injured blood vessels, leading to nuclear dysmorphism and cell senescence in vascular smooth muscle cells (VSMCs). This occurs because PMV adherence reduces intracellular Zn levels, which impairs Zn-dependent processing of prelamin A by the enzyme ZMPSTE24. Consequently, prelamin A accumulates in VSMCs, contributing to the observed nuclear dysmorphism and cell senescence. RNA sequencing and loss-of-function assays revealed that Zinc transporter solute carrier family 39 member 4 (SLC39A4, also called ZIP4) deficiency accounts for the decreased Zinc concentration. Consistently, Zmpste24 and Zmpste24 mice displayed significant cumulative prelamin A, deteriorated nuclear dysmorphism and vascular aging. Whole genome bisulfite sequencing (WGBS) and bioinformatic analysis illustrated that demethylation of genes within Lamina-associated domains (LADs) participates in nuclear dysmorphism and cell senescence. Of note, Zinc supplementation, especially using platelet membrane-coated Zn-MOF nanoparticles, robustly alleviated nuclear dysmorphism and vascular aging. Our data established a novel and significant role of pMVs/ZIP4/zinc/prelamin A axis in promoting nuclear dysmorphism and vascular aging after injury. - Source: PubMed
Ma TengzhiBao HanXu ZhijueRen HeTian WenhaoChen JiaheLiu ZhongqianLu XinwuLv FanYao QingpingQi YingxinHuang Kai