ArticleProceedings of the National Academy of Sciences of the United States of America2007
HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 132 citations in OpenAlex.
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Reduced ZMPSTE24 expression leads to prelamin accumulation and development of steatosis in MASLD patients.Scientific reports · 2025Article
- AIDS patients suffer higher risk of advanced knee osteoarthritis progression due to lopinavir-induced Zmpste24 inhibition.Bone research · 2025Article
- The Compromised Fanconi Anemia Pathway in Prelamin A-Expressing Cells Contributes to Replication Stress-Induced Genomic Instability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Navigating Lipodystrophy: Insights from Laminopathies and Beyond.International journal of molecular sciences · 2024Review
- Review
- 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
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Multiple pathways promote microtubule stabilization in senescent intestinal epithelial cells.npj aging · 2022Article
- Photoswitchable Isoprenoid Lipids Enable Optical Control of Peptide Lipidation.ACS chemical biology · 2022Article
- Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration.Aging cell · 2022Article
- The role of prelamin A post-translational maturation in stress response and 53BP1 recruitment.Frontiers in cell and developmental biology · 2022Article
- Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.Translational research : the journal of laboratory and clinical medicine · 2021Article
- The struggle of a good friend getting old: cellular senescence in viral responses and therapy.EMBO reports · 2021Review
- OMA1-An integral membrane protease?Biochimica et biophysica acta. Proteins and proteomics · 2021Review
- Ste24: An Integral Membrane Protein Zinc Metalloprotease with Provocative Structure and Emergent Biology.Journal of molecular biology · 2020Review
- The tripartite architecture of the eukaryotic integral membrane protein zinc metalloprotease Ste24.Proteins · 2020Article
- Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores.Journal of lipid research · 2020Article
- Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies.JCI insight · 2019Article
3 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
HIV protease inhibitors (HIV-PIs) target the HIV aspartyl protease, which cleaves the HIV gag-pol polyprotein into shorter proteins required for the production of new virions. HIV-PIs are a cornerstone of treatment for HIV but have been associated with lipodystrophy and other side effects. In both human and mouse fibroblasts, we show that HIV-PIs caused an accumulation of prelamin A. The prelamin A in HIV-PI-treated fibroblasts migrated more rapidly than nonfarnesylated prelamin A, comigrating with the farnesylated form of prelamin A that accumulates in ZMPSTE24-deficient fibroblasts. The accumulation of farnesyl-prelamin A in response to HIV-PI treatment was exaggerated in fibroblasts heterozygous for Zmpste24 deficiency. HIV-PIs inhibited the endoproteolytic processing of a GFP-prelamin A fusion protein. The HIV-PIs did not affect the farnesylation of HDJ-2, nor did they inhibit protein farnesyltransferase in vitro. HIV-PIs also did not inhibit the activities of the isoprenyl-cysteine carboxyl methyltransferase ICMT or the prenylprotein endoprotease RCE1 in vitro, but they did inhibit ZMPSTE24 (IC(50): lopinavir, 18.4 +/- 4.6 microM; tipranavir, 1.2 +/- 0.4 microM). We conclude that the HIV-PIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. The inhibition of ZMPSTE24 by HIV-PIs could play a role in the side effects of these drugs.
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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.