The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses reveal that phosphorylation of hTERT at threonine 249 occurs more frequently in aggressive cancers. Using CRISPR/Cas9 genome editing, we introduce substitution mutations at threonine 249 in the endogenous hTERT locus and find that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase and terminal transferase activities. Cap Analysis of Gene Expression (CAGE) demonstrates that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096428 | PMC |
| http://dx.doi.org/10.1038/s41467-020-15289-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
O-GlcNAcylation of enolase 1 serves as a dual regulator of aerobic glycolysis and immune evasion in colorectal cancer.
Proc Natl Acad Sci U S A
October 2024
Department of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Article Synopsis
- Aerobic glycolysis and immune evasion are important characteristics of cancer that are linked through the glycolytic enzyme enolase-1 (ENO1), which undergoes specific modifications known as O-GlcNAcylation.
- Glycosylation at threonine 19 (T19) on ENO1 enhances its glycolytic function, while glycosylation at serine 249 (S249) inhibits its interaction with PD-L1, a protein that helps tumors evade the immune system.
- Targeting the glycosylation of both sites on ENO1 can decrease tumor growth, improve immune response, and may enhance the effectiveness of PD-L1 monoclonal antibody therapy in treating colorectal cancers.
Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells.
Toxicon
October 2024
Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, United States. Electronic address:
Microcystin-LR (MCLR) exposure has been associated with development of hepatocellular carcinoma (HCC). Many of the carcinogenic mechanisms for MCLR have been attributed to the induction of cell survival and proliferation through altered protein phosphorylation pathways by inhibition of protein phosphatases 1 (PP1) and PP2A. The current study determined MCLR effects on the phosphoproteome in human HepaRG cells.
View Article and Find Full Text PDFDual mTOR1/2 Inhibitor Sapanisertib (FTH-003/TAK-228) in Combination With Weekly Paclitaxel in Patients With Previously Treated Metastatic Urothelial Carcinoma: A Phase II Open-Label Study.
Clin Genitourin Cancer
October 2024
Cancer Research Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Medical Oncology, Hospital del Mar, CIBERONC, Barcelona, Spain.
Background: The PI3K/AKT/mTOR pathway is frequently altered at genomic level in metastatic urothelial carcinoma (mUC). Since mTOR is the last protein in the PI3K signaling cascade, it may have the largest impact on the pathway and has been a focus of targeted therapies. Sapanisertib (FTH-003/TAK-228) is an oral highly selective mTOR1 and mTOR2 inhibitor.
View Article and Find Full Text PDFEffects of a diet supplemented with polysaccharides from on growth performance, meat quality, and antioxidant capacity in Chongren Partridge chickens.
Front Vet Sci
May 2024
Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, China.
In this study, the polysaccharides (PCPs) were heteropolysaccharides with molecular weights of 63.17 kDa and 8.99 kDa, and their total carbohydrate content was 76.
View Article and Find Full Text PDFLycopene promoted M2 macrophage polarization via inhibition of NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to Escherichia coli infection in J744A.1 cells.
Arch Microbiol
May 2024
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, 030801, People's Republic of China.
Escherichia coli (E. coli) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!