hTERT antagonizes p53-induced apoptosis independently of telomerase activity

• Published in: Oncogene Vol. 24; no. 8; pp. 1320 - 1327
• Main Authors: RAHMAN, Rubaiyat, LATONEN, Leena, WIMAN, Klas G
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 17.02.2005; Nature Publishing Group
• Subjects: 5-Fluorouracil; Ageing, cell death; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Biological and medical sciences; Burkitt Lymphoma - chemistry; Burkitt Lymphoma - genetics; Burkitt Lymphoma - metabolism; Burkitt's lymphoma; Cancer; Carcinoma - chemistry; Carcinoma - genetics; Carcinoma - metabolism; Cell cycle; Cell growth; Cell Line, Tumor; Cell physiology; Cell survival; Cell Survival - genetics; Cell Survival - physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cloning; Colonic Neoplasms - chemistry; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colorectal cancer; DNA-Binding Proteins; Down-Regulation; Fluorouracil - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation, Neoplastic; Gene regulation; Genes; Humans; Lymphoma; Medicin och hälsovetenskap; Mitomycin - pharmacology; Mitomycin C; Molecular and cellular biology; Mutation - genetics; Oncology; p53 Protein; Proteins; RNA-directed DNA polymerase; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomerase - physiology; Telomerase reverse transcriptase; Temperature; Transcription; Tumor suppressor genes; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - physiology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Tumors; Sweden; TP53 Gene; Enzyme; Carcinogenesis; Telomerase; Apoptosis; Tumor suppressor gene; p53
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208232

The p53 tumor suppressor controls cell growth and survival through transcriptional regulation of gene expression. Previously, we found that the human telomerase reverse transcriptase (hTERT) gene is downregulated by p53. To investigate if hTERT downregulation has a role in p53-dependent apoptosis, we tested if constitutive expression of telomerase could inhibit p53-induced apoptosis. Here we show that constitutive hTERT expression results in increased survival following activation of exogenous temperature-sensitive p53 in BL41 Burkitt lymphoma cells. Similarly, constitutive hTERT expression inhibited wild-type p53-dependent apoptosis in response to mitomycin C or 5-fluorouracil in HCT116 colon carcinoma cells carrying endogenous p53. A telomerase-inactive hTERT mutant was equally efficient in antagonizing p53-induced apoptosis. These findings support the notion that hTERT has antiapoptotic activity and demonstrate that p53-mediated downregulation of hTERT is critical for efficient p53-dependent apoptosis.