ArticleAntioxidants & redox signaling2013
Human GGT2 does not autocleave into a functional enzyme: A cautionary tale for interpretation of microarray data on redox signaling.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Sequence-Only Prediction of Super-Enhancers in Human Cell Lines Using Transformer Models.Biology · 2025Article
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- Genes encoding γ‑glutamyl‑transpeptidases in the allicin biosynthetic pathway in garlic (Biomedical reports · 2024Article
- Distribution ofMolecular vision · 2023Article
- Review
- Metastable HIV-1 Surface Protein Env Sensitizes Cell Membranes to Transformation and Poration by Dual-Acting Virucidal Entry Inhibitors.Biochemistry · 2020Article
- Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.Journal of virology · 2019Article
- γ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1.European journal of human genetics : EJHG · 2018Article
- Non enzymatic upregulation of tissue factor expression by gamma-glutamyl transferase in human peripheral blood mononuclear cells.Thrombosis journal · 2016Article
- Gamma-glutamyl transpeptidase: redox regulation and drug resistance.Advances in cancer research · 2014Review
- Novel insights into eukaryotic γ-glutamyltranspeptidase 1 from the crystal structure of the glutamate-bound human enzyme.The Journal of biological chemistry · 2013Article
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Authors and funding
5 authors.
Funding
Abstract
aimsHuman γ-glutamyltranspeptidase 1 (hGGT1) is a cell-surface enzyme that is a regulator of redox adaptation and drug resistance due to its glutathionase activity. The human GGT2 gene encodes a protein that is 94% identical to the amino-acid sequence of hGGT1. Transcriptional profiling analyses in a series of recent publications have implicated the hGGT2 enzyme as a modulator of disease processes. However, hGGT2 has never been shown to encode a protein with enzymatic activity. The aim of this study was to express the protein encoded by hGGT2 and each of its known variants and to assess their stability, cellular localization, and enzymatic activity.
resultsWe discovered that the proteins encoded by hGGT2 and its variants are inactive propeptides. We show that hGGT2 cDNAs are transcribed with a similar efficiency to hGGT1, and the expressed propeptides are N-glycosylated. However, they do not autocleave into heterodimers, fail to localize to the plasma membrane, and do not metabolize γ-glutamyl substrates. Substituting the coding sequence of hGGT1 to conform to alterations in a CX3C motif encoded by hGGT2 mRNAs disrupted autocleavage of the hGGT1 propeptide into a heterodimer, resulting in loss of plasma membrane localization and catalytic activity. INNOVATION AND
conclusionsThis is the first study to evaluate hGGT2 protein. The data show that hGGT2 does not encode a functional enzyme. Microarray data which have reported induction of hGGT2 mRNA should not be interpreted as induction of a protein that has a role in the metabolism of extracellular glutathione and in maintaining the redox status of the cell.
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