ArticleThe Journal of biological chemistry2008
A potent HIV protease inhibitor, darunavir, does not inhibit ZMPSTE24 or lead to an accumulation of farnesyl-prelamin A in cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- AIDS patients suffer higher risk of advanced knee osteoarthritis progression due to lopinavir-induced Zmpste24 inhibition.Bone research · 2025Article
- The impact of HIV antiretroviral therapy on gut microbiota: the need for well-designed longitudinal studies.Journal of infection in developing countries · 2024Review
- Review
- Prelamin A and ZMPSTE24 in premature and physiological aging.Nucleus (Austin, Tex.) · 2023Review
- Article
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal.Aging cell · 2023Article
- The struggle of a good friend getting old: cellular senescence in viral responses and therapy.EMBO reports · 2021Review
- 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
- MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies.Aging cell · 2018Review
- a-Factor Analogues Containing Alkyne- and Azide-Functionalized Isoprenoids Are Efficiently Enzymatically Processed and Retain Wild-Type Bioactivity.Bioconjugate chemistry · 2018Article
- Formation of a nucleoplasmic reticulum requires de novo assembly of nascent phospholipids and shows preferential incorporation of nascent lamins.Scientific reports · 2017Article
- Human CaaX protease ZMPSTE24 expressed in yeast: Structure and inhibition by HIV protease inhibitors.Protein science : a publication of the Protein Society · 2017Article
- Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24.Nature chemistry · 2016Article
- 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
- HIV protease inhibitors block streptolysin S production.ACS chemical biology · 2015Article
- Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
HIV protease inhibitors (HIV-PIs) are key components of highly active antiretroviral therapy, but they have been associated with adverse side effects, including partial lipodystrophy and metabolic syndrome. We recently demonstrated that a commonly used HIV-PI, lopinavir, inhibits ZMPSTE24, thereby blocking lamin A biogenesis and leading to an accumulation of prelamin A. ZMPSTE24 deficiency in humans causes an accumulation of prelamin A and leads to lipodystrophy and other disease phenotypes. Thus, an accumulation of prelamin A in the setting of HIV-PIs represents a plausible mechanism for some drug side effects. Here we show, with metabolic labeling studies, that lopinavir leads to the accumulation of the farnesylated form of prelamin A. We also tested whether a new and chemically distinct HIV-PI, darunavir, inhibits ZMPSTE24. We found that darunavir does not inhibit the biochemical activity of ZMPSTE24, nor does it lead to an accumulation of farnesyl-prelamin A in cells. This property of darunavir is potentially attractive. However, all HIV-PIs, including darunavir, are generally administered with ritonavir, an HIV-PI that is used to block the metabolism of other HIV-PIs. Ritonavir, like lopinavir, inhibits ZMPSTE24 and leads to an accumulation of prelamin A.
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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.