Ask about this productRelated genes to: GMPPA Blocking Peptide
- Gene:
- GMPPA NIH gene
- Name:
- GDP-mannose pyrophosphorylase A
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-10
- Date modifiied:
- 2016-10-05
Related products to: GMPPA Blocking Peptide
Related articles to: GMPPA Blocking Peptide
- - Source: PubMed
Publication date: 2025/09/19
Qiu XiaoxiaYe ZiqingHuang Ying - GMPPA-Congenital Disorder of Glycosylation (CDG) is an ultra-rare autosomal recessive CDG caused by pathogenic variants in GMPPA that affects the N-linked glycosylation pathway. Affected individuals present with three major symptoms: achalasia, alacrima, and impaired intellectual development during infancy. Current management of GMPPA-CDG is targeted to address patients' symptoms. To date, 23 individuals have been reported with GMPPA-CDG. This paper reviews the clinical, biochemical and genetic characteristics of the reported 23 patients and adds 3 patients with GMPPA-CDG. We also describe the effect of oral N-acetylglucosamine (GlcNAc) supplementation in 3 patients. Besides alacrima, achalasia and developmental/ intellectual disability, we noted in these patients also variable growth impairment, facial dysmorphism, hyperkeratosis, hypohidrosis, anodontia, and hearing deficit. Under treatment with GlcNAc (4-6 g/day), we noted improved tear production in our 3 patients. Given its effect on different developmental pathways, we emphasize the need for multidisciplinary care for this multisystem disorder. We did not find a genotype/phenotype correlation in our cohort of 26 patients. - Source: PubMed
Publication date: 2025/07/18
Altassan RuqaiahAldhahri Sarah KMacdonald GeorgiaShah RameenMorava Eva - GDP-mannose pyrophosphorylase B (GMPPB) loss-of-function is associated with muscular dystrophy and variable additional neurological symptoms. GMPPB facilitates the catalytic conversion of mannose-1-phosphate and GTP to GDP-mannose, which serves as a mannose donor for glycosylation. The activity of GMPPB is regulated by its non-catalytic paralogue GMPPA, which can bind GDP-mannose and interact with GMPPB, thereby acting as an allosteric feedback inhibitor of GMPPB. Using pulldown, immunoprecipitation, turnover experiments as well as immunolabeling and enzyme activity assays, we provide first direct evidence that GMPPB activity is regulated by ubiquitination. We further show that the E3 ubiquitin ligase TRIM67 interacts with GMPPB and that knockdown of TRM67 reduces ubiquitination of GMPPB, thus reflecting a candidate E3 ligase for the ubiquitination of GMPPB. While the inhibition of GMPPB ubiquitination decreases its enzymatic activity, its ubiquitination neither affects its interaction with GMPPA nor its turnover. Taken together, we show that the ubiquitination of GMPPB represents another level of regulation of GDP-mannose supply. - Source: PubMed
Publication date: 2024/06/24
Franzka PatriciaMittag SonnhildChakraborty AbhijnanHuber OtmarHübner Christian A - 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. - Source: PubMed
Publication date: 2024/01/03
Ding Jia-HanXiao YiYang FanSong Xiao-QingXu YingDing Xiao-HongDing RuiShao Zhi-MingDi Gen-HongJiang Yi-Zhou - Glycolytic inhibitor 2-deoxy-d-glucose (2-DG) binds to hexokinase in a non-competitive manner and phosphoglucose isomerase in a competitive manner, blocking the initial steps of the glycolytic pathway. Although 2-DG stimulates endoplasmic reticulum (ER) stress, activating the unfolded protein response to restore protein homeostasis, it is unclear which ER stress-related genes are modulated in response to 2-DG treatment in human primary cells. Here, we aimed to determine whether the treatment of monocytes and monocyte-derived macrophages (MDMs) with 2-DG leads to a transcriptional profile specific to ER stress. - Source: PubMed
Publication date: 2023/06/07
Tamayo-Molina Y SVelilla Paula AHernández-Sarmiento Lady JohanaUrcuqui-Inchima Silvio