APC/CCDH1 synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression

Li, Yang; Yao, Cui-Fang; Xu, Fujiang; Qu, Yuanyuan; Li, Jia-Tao; Lin, Yan; Cao, Ziping; Lin, Peng-Cheng; Xu, Wei; Zhao, Shimin; Zhao, Jin

doi:10.1038/s41467-019-10375-x

Cited by 57 publications

(58 citation statements)

References 55 publications

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“…Proteomics data indicated increased TKT levels in SARS-CoV-2-infected cells, suggesting a role is played by the non-oxidative PPP. Notably, activity of the non-oxidative PPP may not always be a direct consequence of available TKT levels, as TKT activity can be strongly increased by heterodimer formation with transketolase-like 1 (TKTL1) [ 18 ]. However, anti-SARS-CoV-2 effects exerted by the TKT inhibitor BOT suggest that TKT and the non-oxidative PPP are functionally involved in SARS-CoV-2 replication.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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SARS-CoV-2 is causing the coronavirus disease 2019 (COVID-19) pandemic, for which effective pharmacological therapies are needed. SARS-CoV-2 induces a shift of the host cell metabolism towards glycolysis, and the glycolysis inhibitor 2-deoxy-d-glucose (2DG), which interferes with SARS-CoV-2 infection, is under development for the treatment of COVID-19 patients. The glycolytic pathway generates intermediates that supply the non-oxidative branch of the pentose phosphate pathway (PPP). In this study, the analysis of proteomics data indicated increased transketolase (TKT) levels in SARS-CoV-2-infected cells, suggesting that a role is played by the non-oxidative PPP. In agreement, the TKT inhibitor benfooxythiamine (BOT) inhibited SARS-CoV-2 replication and increased the anti-SARS-CoV-2 activity of 2DG. In conclusion, SARS-CoV-2 infection is associated with changes in the regulation of the PPP. The TKT inhibitor BOT inhibited SARS-CoV-2 replication and increased the activity of the glycolysis inhibitor 2DG. Notably, metabolic drugs like BOT and 2DG may also interfere with COVID-19-associated immunopathology by modifying the metabolism of immune cells in addition to inhibiting SARS-CoV-2 replication. Hence, they may improve COVID-19 therapy outcomes by exerting antiviral and immunomodulatory effects.

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Section: Discussionmentioning

confidence: 99%

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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“…Besides this TKTL1 enables the production of Acetyl-CoA, a central metabolic building block for lipids. Recently, it has been demonstrated that TKTL1 controls cell cycle [12]. Upregulation of TKTL1 is associated with poor prognosis in colon and urothelial cancer as well as rectum and lung carcinoma [10,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma

Saman

Stagno

Warmann

et al. 2019

CBM

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OBJECTIVE: The EDIM (Epitope detection in monocytes) blood test is based on two biomarkers Apo10 and TKTL1. Apo10 is responsible for cell proliferation and resistance to apoptosis. TKTL1 plays a major role in anaerobic glycolysis of tumor cells, leading to destruction of the basal membrane and metastasis as well as in controlling cell cycle. For the first time we analyzed Apo10 and TKLT1 in patients with cholangiocellular (CCC), pancreatic (PC), and colorectal carcinoma (CRC). METHODS: Blood samples of 62 patients with CCC, PC, and CRC were measured and compared to 29 control patients. We also investigated 13 patients with inflammatory conditions, because elevated TKTL1 and Apo10 have been previously described in affected individuals. Flow cytometry was used to detect surface antigens CD14 + /CD16 + (activated monocytes/macrophages). Percentages of macrophages harboring TKTL1 and Apo10 were determined. A combined EDIM score (EDIM-CS: TKTL1 plus Apo10) was calculated. Results were correlated with serum tumor markers CEA and CA19-9. RESULTS: Patients with CCC had 100% positive EDIM-CS but CEA and CA19-9 were positive in only 22.2% and 70%, respectively. Patients with PC had 100% positive EDIM-CS but positive tumor markers in only 37.5% (CEA) and 72.7% (CA19-9). Patients with CRC had 100% positive EDIM-CS but only 50% positive CEA. EDIM-CS was positive in 100% (62/62) of all cancer patients and in 0% of healthy individuals. Of the individuals with inflammation, 7.7% had a positive EDIM-CS. CONCLUSION: The sensitivity of the EDIM blood test and the comparison with traditional tumor markers indicate that this new test might improve the detection of carcinomas (CCC, PC and, CRC) and might be relevant for the diagnosis of all tumor entities.

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“…A study published in 2019 revealed the regulation mechanism of pentose phosphate-related metabolism in tumour cells, which targets the adjustment of the tumour's cell cycle, affecting the energy requirement of tumour cells [38] . Other studies pointed out that ribosomes involved in epithelial-mesenchymal transition accelerate the metastasis of cancer cells [39] and that chemokines have a regulatory role in immune cell recruitment and tumour and stromal cell biology [40] .…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of m6A RNA Methylation Modulators and Potential Clinical Application in Pancreatic Cancer

Wang

et al. 2020

Preprint

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Background m6A is the most prevalent and abundant form of mRNA modification and plays a dual role in cancer development. The high incidence and mortality of pancreatic cancer are critical obstacles worldwide. In this study, we investigated the function of m6A RNA methylation modulators in pancreatic cancer. Methods Expression of 13 m6A RNA methylation modulators and clinical data from patients with pancreatic adenocarcinoma were obtained from TCGA database. Differences in the expression of 13 m6A RNA methylation modulators between tumour (n = 178) and healthy (n = 4) samples were compared by Wilcoxon test. LASSO Cox regression was used to select m6A RNA methylation modulators for analysis of the relationship between expression and clinical characteristics by univariate and multivariate regression. The pathways of the m6A RNA methylation modulators were examined by gene set enrichment analysis (GSEA) and we found enrichment in chemokine, ribosome, and mTOR signalling pathways. Results WTAP had a low expression in tumour samples compared with healthy samples. Furthermore, our analyses revealed that the m6A RNA methylation modulators YTHDF1, ALKBH5, METTL3, METTL14, and KIAA1429 correlated with high-risk patients, resulting in an elevated risk score and a lower overall survival. High-risk score correlated with clinical characteristic and was an independent prognostic indicator for pancreatic adenocarcinoma. The pathways involved were identified by GSEA to explore the potential mechanism of action. Conclusion Modulators involved in m6A RNA methylation were associated with the development of pancreatic cancer. A risk score based on the expression of YTHDF1, ALKBH5, METTL3, METTL14, and KIAA1429 may be an independent prognostic indicator.

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APC/CCDH1 synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression

Cited by 57 publications

References 55 publications

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma

Prognostic Value of m6A RNA Methylation Modulators and Potential Clinical Application in Pancreatic Cancer

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