Proteins CRF21, Human
- Known as:
- Proteins CRF21, Human
- Catalog number:
- C214
- Product Quantity:
- 10μg
- Category:
- -
- Supplier:
- Novoprotein
- Gene target:
- Proteins CRF21 Human
Related genes to: Proteins CRF21, Human
- Gene:
- GGCT NIH gene
- Name:
- gamma-glutamylcyclotransferase
- Previous symbol:
- C7orf24, GCTG
- Synonyms:
- MGC3077, CRF21, Ggc
- Chromosome:
- 7p14.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-14
- Date modifiied:
- 2017-12-15
Related products to: Proteins CRF21, Human
Related articles to: Proteins CRF21, Human
- Glioblastoma is the most aggressive and treatment-resistant brain tumor. Ferroptosis, an iron-dependent form of regulated cell death caused by lipid peroxidation, has emerged as a promising therapeutic strategy; however, intrinsic resistance to ferroptosis limits its therapeutic efficacy. Here, we demonstrate that metabolic depletion of cysteine through dual inhibition of exogenous and endogenous sources represents a novel approach to overcome this resistance. While inhibition of xCT suppresses cystine uptake and induces ferroptosis, we identified γ-glutamylcyclotransferase (GGCT), a key enzyme in glutathione (GSH) degradation, as a metabolic compensation pathway that regenerates cysteine to sustain redox homeostasis. Blocking both xCT and GGCT synergistically depleted intracellular cysteine and GSH, leading to excessive accumulation of reactive oxygen species (ROS), lipid peroxidation, and ferroptotic cell death in glioblastoma cells. Importantly, dual inhibition markedly suppressed tumor growth in vivo and enhanced oxidative stress in tumor tissues, as evidenced by 4-hydroxynonenal accumulation. These findings uncover a previously unrecognized mechanism by which GGCT confers ferroptosis resistance by maintaining intracellular redox balance. Targeting the xCT-GGCT axis effectively disrupts redox homeostasis and eliminates metabolic plasticity that underlies ferroptosis resistance in glioblastoma. This study provides a mechanistic and translational rationale for developing dual inhibition of xCT and GGCT as a promising therapeutic strategy against this lethal and therapy-refractory cancer. - Source: PubMed
Publication date: 2026/04/15
Mori MasayaIi HiromiMatsumura MaiSone YuhiKumamoto HarunaSakurai KanaFujino TerunaNihei NanamiHongo NanaNose KozueMatsumoto TakahiroFujita MitsuguNakata Susumu - γ-Glutamylcyclotransferase (GGCT) is a highly expressed protein in various cancers, and its knockdown and inhibitors suppress the growth of cancer cells in vitro and in vivo. Although GGCT is a promising target for anti-cancer strategies, no drugs have progressed to clinical availability yet. We established a novel target-based and cell-based screening method for GGCT inhibitors, enabling the efficient discovery of compounds that inhibit intracellular GGCT activity. Using the chemiluminogenic probe LISA-103 in response to GGCT enzymatic activity, high-throughput screening for GGCT inhibitors was performed in lung cancer SW1573 cells. The hit compound plumbagin was identified as a novel GGCT inhibitor that suppressed its activity intracellularly. Plumbagin directly bound to a GGCT-recombinant protein and inhibited its activity. Moreover, plumbagin up-regulated p21, a cyclin-dependent kinase inhibitor, and activated the tumor suppressor RB protein, inhibiting cell growth and cell cycle progression in breast MCF7 and colon HCT116 cancer cell lines. These phenomena induced by plumbagin mimicked the effect of GGCT depletion. The treatment with plumbagin suppressed tumor growth of HCT116 xenograft mice. These results suggest the potential of plumbagin in cancer therapy as a GGCT inhibitor. - Source: PubMed
Publication date: 2026/04/13
Taniguchi KeikoNohara YukieHorinaka ManoNose KozueMori MasayaIi HiromiKawakami HirokoYano KazutoNakata SusumuYoshiya TakuSakai Toshiyuki - Glutamine (Gln) metabolism serves dual metabolic roles: it fuels the tricarboxylic acid (TCA) cycle, while concurrently sustaining redox balance through glutathione (GSH) synthesis. γ-Glutamylcyclotransferase (GGCT), a key metabolic enzyme frequently overexpressed in various cancers, has an undefined role in directing glutamine metabolic flux during tumorigenesis. This study demonstrated that glutamine promotes cancer cell growth by regulating GSH and reactive oxygen species (ROS) levels, with this process being closely associated with GGCT expression. Knockdown of GGCT significantly inhibited tumor growth, depleted GSH, and elevated ROS levels, whereas overexpression of GGCT exerted the opposite effects. Furthermore, we refined and established the Gln/c-Myc/miR-29b-3p/GGCT regulatory axis. Notably, GGCT knockdown markedly altered mitochondrial morphology and impaired oxidative phosphorylation and glycolysis capacity. Targeted metabolomics analysis revealed that GGCT knockdown significantly reduced the abundance of TCA cycle intermediates, while GGCT overexpression substantially increased their levels. [U-C]glutamine isotope tracing experiments showed that GGCT overexpression reduced Gln contribution to the TCA cycle and diverted it preferentially to the GSH synthesis pathway for ROS regulation. In contrast, [U-C]glucose isotope tracing results demonstrated a significant increase in TCA cycle intermediates derived from glucose when GGCT was overexpressed. Additional, supplementation of sodium pyruvate and JX06 in GGCT-knockdown cells confirmed that this regulatory effect of GGCT-mediated changes in ROS was independent of energy metabolism pathways. Collectively, this study identifies GGCT as a metabolic switch that diverts Gln flux toward GSH synthesis to maintain redox homeostasis, while enhancing glucose-fueled anaplerosis into the TCA cycle to sustain cell proliferation. These findings highlight GGCT as a potential therapeutic target for disrupting cancer redox adaptation and metabolic plasticity. - Source: PubMed
Publication date: 2026/03/24
Yang LijunSun HandiWang RuonanYang DepengGu QiZhao GuipingSun LipingChen XingheLv JianxinLin XiaoyuCheng JiahuiAkhtar Muhammad LuqmanZhang MengmengZang JingyuShi XinyueZhang ZihaoDeng LijunXiao LixingYue LeiDong WeiJiang QinghuaHan FangLi YuNie Huan - Chronic rhinosinusitis with nasal polyps (CRSwNP) in children is a clinically significant inflammatory disorder characterized by persistent symptoms and complex underlying mechanisms. This study used multi-omics approaches to investigate potential microbial and metabolic associations in pediatric CRSwNP. - Source: PubMed
Publication date: 2026/01/25
Jia ChaoLiu XiaogeLiu WenjingYao XingfengChen XiaoxuZhao JinhaoWang PengpengGe WentongHan Yang - γ-Glutamylcyclotransferase (GGCT) depletion suppresses breast cancer cell proliferation by inducing cellular senescence. However, the underlying molecular mechanisms have not been fully elucidated. Therefore, the objective of this study was to elucidate the mechanisms by which GGCT depletion suppresses cancer cell proliferation. - Source: PubMed
Kubota ShigehisaIi HiromiIsono TakahiroKusaba TakutoNagasawa MasayukiWada AkinoriKobayashi KenichiYamanaka KazuakiMori MasayaTaniguchi KeikoNakata SusumuKageyama Susumu