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Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment.

Kageyama S, Hanada E, Ii H, Tomita K, Yoshiki T, Kawauchi A - Biomed Res Int (2015)

Bottom Line: Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism.However, its gene locus was unknown for many years.Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.

ABSTRACT
Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism. However, its gene locus was unknown for many years. Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein. Orthologs have been found in bacteria, plants, and nematodes as well as higher organisms, and the GGCT gene is highly preserved among a wide range of species. GGCT (C7orf24) was also reported as an upregulated protein in various cancers. Although the function of GGCT in cancer cells has not been determined, the following important activities have been reported: (1) high expression in various cancer tissues and cancer cell lines, (2) low expression in normal tissues, (3) inhibition of cancer cell proliferation via anti-GGCT RNAi, (4) inhibition of cancer cell invasion and migration via anti-GGCT RNAi, (5) an epigenetic transcriptional regulation in cancer cells, and (6) an antitumor effect in cancer-bearing xenograft mice. Therefore, GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings.

No MeSH data available.


Related in: MedlinePlus

γ-glutamyl cycle. GGCT, gamma-glutamylcyclotransferase; GGT, gamma-glutamyltranspeptidase; GCL, glutamate cysteine ligase; GS, glutathione synthase; OPLAH, 5-oxoprolinase; γ-Glu-Cys-Gly, glutathione; DP, dipeptidase.
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Related In: Results  -  Collection


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fig1: γ-glutamyl cycle. GGCT, gamma-glutamylcyclotransferase; GGT, gamma-glutamyltranspeptidase; GCL, glutamate cysteine ligase; GS, glutathione synthase; OPLAH, 5-oxoprolinase; γ-Glu-Cys-Gly, glutathione; DP, dipeptidase.

Mentions: GGCT is one of the major enzymes comprising the gamma-glutamyl cycle proposed by Orlowski et al. (Figure 1) [2]. GGCT catalyzes the reaction producing 5-oxoproline and free amino acids from gamma-glutamyl peptide taken into the cell. Orthologs of GGCT range from bacteria, plants, and nematodes to higher organisms, and the GGCT gene is highly preserved among a wide range of species.


Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment.

Kageyama S, Hanada E, Ii H, Tomita K, Yoshiki T, Kawauchi A - Biomed Res Int (2015)

γ-glutamyl cycle. GGCT, gamma-glutamylcyclotransferase; GGT, gamma-glutamyltranspeptidase; GCL, glutamate cysteine ligase; GS, glutathione synthase; OPLAH, 5-oxoprolinase; γ-Glu-Cys-Gly, glutathione; DP, dipeptidase.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4538363&req=5

fig1: γ-glutamyl cycle. GGCT, gamma-glutamylcyclotransferase; GGT, gamma-glutamyltranspeptidase; GCL, glutamate cysteine ligase; GS, glutathione synthase; OPLAH, 5-oxoprolinase; γ-Glu-Cys-Gly, glutathione; DP, dipeptidase.
Mentions: GGCT is one of the major enzymes comprising the gamma-glutamyl cycle proposed by Orlowski et al. (Figure 1) [2]. GGCT catalyzes the reaction producing 5-oxoproline and free amino acids from gamma-glutamyl peptide taken into the cell. Orthologs of GGCT range from bacteria, plants, and nematodes to higher organisms, and the GGCT gene is highly preserved among a wide range of species.

Bottom Line: Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism.However, its gene locus was unknown for many years.Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.

ABSTRACT
Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism. However, its gene locus was unknown for many years. Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein. Orthologs have been found in bacteria, plants, and nematodes as well as higher organisms, and the GGCT gene is highly preserved among a wide range of species. GGCT (C7orf24) was also reported as an upregulated protein in various cancers. Although the function of GGCT in cancer cells has not been determined, the following important activities have been reported: (1) high expression in various cancer tissues and cancer cell lines, (2) low expression in normal tissues, (3) inhibition of cancer cell proliferation via anti-GGCT RNAi, (4) inhibition of cancer cell invasion and migration via anti-GGCT RNAi, (5) an epigenetic transcriptional regulation in cancer cells, and (6) an antitumor effect in cancer-bearing xenograft mice. Therefore, GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings.

No MeSH data available.


Related in: MedlinePlus