ArticleJournal of lipid research2012
Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation in cells by inhibiting ZMPSTE24.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Progerin cross-linking stiffens the nucleus and impairs mechanosensation in Hutchinson-Gilford progeria syndrome.Journal of cell science · 2026Article
- Article
- Roles of the lamin A-specific tail region in the localization to sites of nuclear envelope rupture.PNAS nexus · 2024Article
- Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.Nature communications · 2024Article
- Progeroid syndrome patients with ZMPSTE24 deficiency could benefit when treated with rapamycin and dimethylsulfoxide.Cold Spring Harbor molecular case studies · 2017Article
- LMNA missense mutations causing familial partial lipodystrophy do not lead to an accumulation of prelamin A.Nucleus (Austin, Tex.) · 2016Article
- AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Glucotoxic and diabetic conditions induce caspase 6-mediated degradation of nuclear lamin A in human islets, rodent islets and INS-1 832/13 cells.Apoptosis : an international journal on programmed cell death · 2014Article
- Identification of a farnesol analog as a Ras function inhibitor using both an in vivo Ras activation sensor and a phenotypic screening approach.Molecular and cellular biochemistry · 2014Article
- Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.PloS one · 2014Article
- Human isoprenoid synthase enzymes as therapeutic targets.Frontiers in chemistry · 2014Review
- Glucotoxic conditions induce endoplasmic reticulum stress to cause caspase 3 mediated lamin B degradation in pancreatic β-cells: protection by nifedipine.Biochemical pharmacology · 2013Article
- Efficient use of exogenous isoprenols for protein isoprenylation by MDA-MB-231 cells is regulated independently of the mevalonate pathway.The Journal of biological chemistry · 2013Article
- Nifedipine prevents etoposide-induced caspase-3 activation, prenyl transferase degradation and loss in cell viability in pancreatic β-cells.Apoptosis : an international journal on programmed cell death · 2013Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Protein farnesyltransferase (FTase) inhibitors, generally called "FTIs," block the farnesylation of prelamin A, inhibiting the biogenesis of mature lamin A and leading to an accumulation of prelamin A within cells. A recent report found that a GGTI, an inhibitor of protein geranylgeranyltransferase-I (GGTase-I), caused an exaggerated accumulation of prelamin A in the presence of low amounts of an FTI. This finding was interpreted as indicating that prelamin A can be alternately prenylated by GGTase-I and that inhibiting both protein prenyltransferases leads to more prelamin A accumulation than blocking FTase alone. Here, we tested an alternative 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). In our studies, commonly used GGTIs caused prelamin A accumulation in human fibroblasts, but the prelamin A in GGTI-treated cells exhibited a more rapid electrophoretic mobility than prelamin A from FTI-treated cells. The latter finding suggested that the prelamin A in GGTI-treated cells might be farnesylated (which would be consistent with the notion that GGTIs inhibit ZMPSTE24). Indeed, metabolic labeling studies revealed that the prelamin A in GGTI-treated fibroblasts is farnesylated. Moreover, biochemical assays of ZMPSTE24 activity showed that ZMPSTE24 is potently inhibited by a GGTI. Our studies show that GGTIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. Thus, caution is required when interpreting the effects of GGTIs on prelamin A processing.
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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.