ArticleMolecular cancer research : MCR2008
The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both regulated and controls colony-stimulating factor-1 messenger RNA stability in ovarian cancer.
Article in Molecular cancer research : MCR, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 105 citations in OpenAlex.
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- Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer.Genes & diseases · 2024Article
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- Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options.Current oncology (Toronto, Ont.) · 2023Review
- A novel colony-stimulating factor 1 (CSF1) translocation involving human endogenous retroviral element in a tenosynovial giant cell tumor.Genes, chromosomes & cancer · 2023Article
- The mutual interaction of glycolytic enzymes and RNA in post-transcriptional regulation.RNA (New York, N.Y.) · 2022Review
- The uncommon function and mechanism of the common enzyme glyceraldehyde-3-phosphate dehydrogenase in the metamorphosis ofFrontiers in bioengineering and biotechnology · 2022Article
- The search for RNA-binding proteins: a technical and interdisciplinary challenge.Biochemical Society transactions · 2021Review
- Phosphoglycerate kinase: structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea.Open biology · 2020Review
- Metabolic signaling in T cells.Cell research · 2020Review
- IDH1 fine-tunes cap-dependent translation initiation.Journal of molecular cell biology · 2019Article
- Structural Study of Monomethyl Fumarate-Bound Human GAPDH.Molecules and cells · 2019Article
- Proteome profiling of low grade serous ovarian cancer.Journal of ovarian research · 2019Article
- A dedicated glyceraldehyde-3-phosphate dehydrogenase is involved in the biosynthesis of volatile sesquiterpenes in Trichoderma virens-evidence for the role of a fungal GAPDH in secondary metabolism.Current genetics · 2019Article
- Identification of Key Pathways and Genes of Acute Respiratory Distress Syndrome Specific Neutrophil Phenotype.BioMed research international · 2019Article
- Emerging Evidence of Translational Control by AU-Rich Element-Binding Proteins.Frontiers in genetics · 2019Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU-rich elements has long been known, the expected connection between GAPDH and control of mRNA stability has never been made. Recently, we described GAPDH binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3' untranslated region (UTR), which we showed to be an mRNA decay element in ovarian cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients with ovarian cancer. We investigated the functional significance of GAPDH's association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half-lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates with a large AU-rich-containing region. The effects of binding of GAPDH protein or ovarian extracts to mutations of the AU-rich regions within the footprint were consistent with this finding. In a tissue array containing 256 ovarian and fallopian tube cancer specimens, we found that GAPDH was regulated in these cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008). In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. We are the first to evaluate the clinical role of GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is regulated, and we now recognize that one of the many functions of GAPDH is to promote mRNA stability of CSF-1, an important cytokine in tumor progression.
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