GMPPA

Last update 08 May 2025

Basic Info

Synonyms

GDP-mannose pyrophosphorylase A, GMPP-alpha, GMPPA

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Introduction

Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex (PubMed:24035193, PubMed:33986552). Mediates allosteric feedback inhibition of GMPPB catalytic activity upon binding GDP-alpha-D-mannose (PubMed:24035193, PubMed:33986552). Together with GMPPB regulates GDP-alpha-D-mannose levels (PubMed:33986552).

100 Clinical Results associated with GMPPA

100 Translational Medicine associated with GMPPA

0 Patents (Medical) associated with GMPPA

Literatures (Medical) associated with GMPPA

01 Dec 2024·International Journal of Biological Macromolecules

Carbon starvation drives biosynthesis of high mannose-composition polysaccharides in Ganoderma lucidum

Article

Author: Xu, Mengmeng ; Zhao, Liting ; Shi, Guiyang ; Shen, Mengye ; Chen, Lei ; Ding, Zhongyang ; Li, Junxun ; Liu, Jingyun

Polysaccharides with high mannose composition exhibit favorable antitumor activity, but there is currently a lack of well-defined and practical approaches to efficiently manufacture this type of polysaccharide. This study explores the impact of carbon utilization on exopolysaccharide (EPS) production and monosaccharide composition in Ganoderma lucidum, aiming to promote the biosynthesis of polysaccharides with high mannose composition. Sucrose supply significantly increased the mannose proportion to 35.52 % in EPS via carbon starvation. To enhance polysaccharide production with high mannose composition, a joint control by carbon starvation and glucose feeding strategy was developed, achieving 0.42 g/L EPS and 18.67 % mannose with 5 g/L glucose supplementation on day 6 in an initial 10 g/L glucose medium. Using this approach, G. lucidum mycelia exhibited normal growth patterns similar to those in sucrose culture. Essentially, carbon starvation upregulated key genes in the GDP-mannose synthesis pathway, including phosphomannose isomerase (PMI), phosphomannose mutase (PMM), and GDP-mannose pyrophosphorylase (GMP), by over 2-fold, facilitating high mannose-composition polysaccharide synthesis in both sucrose and carbon starvation conditions. This work provides insights into the biosynthesis of structurally specific polysaccharides in G. lucidum and offers a foundation for developing polysaccharides with diverse applications in food, medicine, and other fields.

03 Jan 2024·Science Translational MedicineQ1 · MEDICINE

Guanosine diphosphate–mannose suppresses homologous recombination repair and potentiates antitumor immunity in triple-negative breast cancer

Q1 · MEDICINE

Article

Author: Ding, Xiao-Hong ; Ding, Jia-Han ; Shao, Zhi-Ming ; Yang, Fan ; Jiang, Yi-Zhou ; Xu, Ying ; Di, Gen-Hong ; Ding, Rui ; Song, Xiao-Qing ; Xiao, Yi

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis. TNBCs with high homologous recombination deficiency (HRD) scores benefit from DNA-damaging agents, including platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, whereas those with low HRD scores still lack therapeutic options. Therefore, we sought to exploit metabolic alterations to induce HRD and sensitize DNA-damaging agents in TNBCs with low HRD scores. We systematically analyzed TNBC metabolomics and identified a metabolite, guanosine diphosphate (GDP)–mannose (GDP-M), that impeded homologous recombination repair (HRR). Mechanistically, the low expression of the upstream enzyme GDP-mannose-pyrophosphorylase-A (GMPPA) led to the endogenous up-regulation of GDP-M in TNBC. The accumulation of GDP-M in tumor cells further reduced the interaction between breast cancer susceptibility gene 2 (BRCA2) and ubiquitin-specific peptidase 21 (USP21), which promoted the ubiquitin-mediated degradation of BRCA2 to inhibit HRR. Therapeutically, we illustrated that the supplementation of GDP-M sensitized DNA-damaging agents to impair tumor growth in both in vitro (cancer cell line and patient-derived organoid) and in vivo (xenograft in immunodeficient mouse) models. Moreover, the combination of GDP-M with DNA-damaging agents activated STING-dependent antitumor immunity in immunocompetent syngeneic mouse models. Therefore, GDP-M supplementation combined with PARP inhibition augmented the efficacy of anti–PD-1 antibodies. Together, these findings suggest that GDP-M is a crucial HRD-related metabolite and propose a promising therapeutic strategy for TNBCs with low HRD scores using the combination of GDP-M, PARP inhibitors, and anti–PD-1 immunotherapy.

28 Sep 2023·International journal of molecular sciences

Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.

Article

Author: Huang, Zi-Lu ; Hu, Yu-Jun ; Xiao, Xiang ; Chen, Zhong-Ping ; Liu, Ya ; Yu, Yan-Jiao ; Zheng, Shuo-Han ; Liu, Song-Ran ; Feng, Ping ; Xia, Yun-Fei ; Shen, Guang-Xin ; Suarez, Milagros ; Li, Xiao-Nan ; Abdallah, Aalaa Sanad ; Wang, Ying

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

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