| Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT. | |
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MedLine Citation:
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PMID: 20453884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, we identified posttranslational regulation of human telomerase reverse-transcriptase (hTERT) by the E3 ligase Hdm2. The telomerase activity generated by exogenous hTERT in U2OS cells was reduced on adriamycin treatment. The overexpressed levels of hTERT were also decreased under the same conditions. These processes were reversed by treatment with a proteasome inhibitor or depletion of Hdm2. Furthermore, intrinsic telomerase activity was increased in HCT116 cells with ablation of Hdm2. Immunoprecipitation analyses showed that hTERT and Hdm2 bound to each other in multiple domains. Ubiquitination analyses showed that Hdm2 could polyubiquitinate hTERT principally at the N-terminus, which was further degraded in a proteasome-dependent manner. An hTERT mutant with all five lysine residues at the N-terminus of hTERT that mutated to arginine became resistant to Hdm2-mediated ubiquitination and degradation. In U2OS cells, depletion of Hdm2 or addition of the Hdm2-resistant hTERT mutant strengthened the cellular protective effects against apoptosis. Similar results were obtained with the Hdm2-stable H1299 cell line. These observations indicate that Hdm2 is an E3 ligase of hTERT. |
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Authors:
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W Oh; E-W Lee; D Lee; M-R Yang; A Ko; C-H Yoon; H-W Lee; Y-S Bae; C Y Choi; J Song |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-10 |
Journal Detail:
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Title: Oncogene Volume: 29 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-15 Completed Date: 2010-08-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 4101-12 Citation Subset: IM |
Affiliation:
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Department of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Humans Immunoprecipitation Lysine / metabolism Proto-Oncogene Proteins c-mdm2 / physiology* Telomerase / chemistry, metabolism* Ubiquitin-Protein Ligases / metabolism* Ubiquitination |
| Chemical | |
Reg. No./Substance:
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56-87-1/Lysine; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2; EC 6.3.2.19/Ubiquitin-Protein Ligases |
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