ArticleOncotarget2016
MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state.
Article in Oncotarget, 2016. 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, 44 citations in OpenAlex.
- NAA40 and NAC cooperate in co-translational histone acetylation in humans.Nature communications · 2026Article
- Structural basis of co-translational N-myristoylation in humans.Nature communications · 2026Article
- Profiling the Complexity of Resistance Factors in Cancer Cells Towards Berberine and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Methionine Aminopeptidase 2 (MetAP2) Inhibitor BL6 Attenuates Inflammation in Cultured Microglia and in a Mouse Model of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Article
- Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.Circulation research · 2025Article
- Destined for destruction: The role of methionine aminopeptidases and plant cysteine oxidases in N-degron formation.Plant physiology · 2024Review
- Antimalarial activity of borrelidin and fumagilin inOpen veterinary journal · 2024Article
- Drug targeting of aminopeptidases: importance of deploying a right metal cofactor.Biophysical reviews · 2024Review
- Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models.Molecular cancer therapeutics · 2024Article
- Repurposing of the Drug Tezosentan for Cancer Therapy.Current issues in molecular biology · 2023Review
- System-wide analyses reveal essential roles of N-terminal protein modification in bacterial membrane integrity.iScience · 2022Article
- Degradome-focused RNA interference screens to identify proteases important for breast cancer cell growth.Frontiers in oncology · 2022Article
- Methionine aminopeptidase 2 as a potential target in pancreatic ductal adenocarcinoma.American journal of translational research · 2022Article
- A brain proteomic signature of incipient Alzheimer's disease in youngScience advances · 2021Article
- Structural and Functional Basis of Potent Inhibition of Leishmanial Leucine Aminopeptidase by Peptidomimetics.ACS omega · 2021Article
- In vitro study on aspects of molecular mechanisms underlying invasive aspergillosis caused by gliotoxin and fumagillin, alone and in combination.Scientific reports · 2020Article
- Dual lysine and N-terminal acetyltransferases reveal the complexity underpinning protein acetylation.Molecular systems biology · 2020Article
- MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity.JCI insight · 2020Article
- Fumagillin, a Mycotoxin ofToxins · 2019Review
- LINC00461 affects the survival of patients with renal cell carcinoma by acting as a competing endogenous RNA for microRNA‑942.Oncology reports · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fumagillin and its derivatives are therapeutically useful because they can decrease cancer progression. The specific molecular target of fumagillin is methionine aminopeptidase 2 (MetAP2), one of the two MetAPs present in the cytosol. MetAPs catalyze N-terminal methionine excision (NME), an essential pathway of cotranslational protein maturation. To date, it remains unclear the respective contribution of MetAP1 and MetAP2 to the NME process in vivo and why MetAP2 inhibition causes cell cycle arrest only in a subset of cells. Here, we performed a global characterization of the N-terminal methionine excision pathway and the inhibition of MetAP2 by fumagillin in a number of lines, including cancer cell lines. Large-scale N-terminus profiling in cells responsive and unresponsive to fumagillin treatment revealed that both MetAPs were required in vivo for M[VT]X-targets and, possibly, for lower-level M[G]X-targets. Interestingly, we found that the responsiveness of the cell lines to fumagillin was correlated with the ability of the cells to modulate their glutathione homeostasis. Indeed, alterations to glutathione status were observed in fumagillin-sensitive cells but not in cells unresponsive to this agent. Proteo-transcriptomic analyses revealed that both MetAP1 and MetAP2 accumulated in a cell-specific manner and that cell sensitivity to fumagillin was related to the levels of these MetAPs, particularly MetAP1. We suggest that MetAP1 levels could be routinely checked in several types of tumor and used as a prognostic marker for predicting the response to treatments inhibiting MetAP2.
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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.