ArticleBiochemical and biophysical research communications2008
HIV-protease inhibitors block the enzymatic activity of purified Ste24p.
Article in Biochemical and biophysical research communications, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Drug-Induced Atypical Lipodystrophy.JCEM case reports · 2024Article
- Prelamin A and ZMPSTE24 in premature and physiological aging.Nucleus (Austin, Tex.) · 2023Review
- OMA1-An integral membrane protease?Biochimica et biophysica acta. Proteins and proteomics · 2021Review
- Lipodystrophies-Disorders of the Fatty Tissue.International journal of molecular sciences · 2020Review
- Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores.Journal of lipid research · 2020Article
- a-Factor Analogues Containing Alkyne- and Azide-Functionalized Isoprenoids Are Efficiently Enzymatically Processed and Retain Wild-Type Bioactivity.Bioconjugate chemistry · 2018Article
- 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
- Lipodystrophy Syndromes.Endocrinology and metabolism clinics of North America · 2016Review
- Lamin A/C deficiency is an independent risk factor for cervical cancer.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies.Journal of human genetics · 2014Review
- Structure of the integral membrane protein CAAX protease Ste24p.Science (New York, N.Y.) · 2013Article
- The HIV-1 protease inhibitor nelfinavir activates PP2 and inhibits MAPK signaling in macrophages: a pathway to reduce inflammation.Journal of leukocyte biology · 2012Article
- Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity.Human molecular genetics · 2012Article
- Leptin revisited: its mechanism of action and potential for treating diabetes.Nature reviews. Drug discovery · 2012Review
- Biogenesis of the Saccharomyces cerevisiae pheromone a-factor, from yeast mating to human disease.Microbiology and molecular biology reviews : MMBR · 2012Review
- Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation in cells by inhibiting ZMPSTE24.Journal of lipid research · 2012Article
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- The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α.Journal of cell science · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We reported that several HIV protease inhibitors (HIV-PIs) interfere with the endoproteolytic processing of two farnesylated proteins, yeast a-factor and mammalian prelamin A. We proposed that these drugs interfere with prelamin A processing by blocking ZMPSTE24, an integral membrane zinc metalloproteinase known to play a critical role in its processing. However, because all of the drug inhibition studies were performed with cultured fibroblasts or crude membrane fractions rather than on purified enzyme preparations, no definitive conclusions could be drawn. Here, we purified Ste24p, the yeast ortholog of ZMPSTE24, and showed that its enzymatic activity was blocked by three HIV-PIs (lopinavir, ritonavir, and tipranavir). A newer HIV-PI, darunavir, had little effect on Ste24p activity. None of the HIV-PIs had dramatic effects on the enzymatic activity of purified Ste14p, the prenylprotein methyltransferase. These studies strongly support our hypothesis that HIV-PIs block prelamin A processing by directly affecting the enzymatic activity of ZMPSTE24, and in this way they may contribute to lipodystrophy in individuals undergoing HIV-PI treatment.
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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.