Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)4101-4112
Number of pages12
JournalOncogene
Volume29
Issue number28
DOIs
Publication statusPublished - 2010 Jul 1

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Ubiquitin-Protein Ligases
Telomerase
Ubiquitination
HCT116 Cells
human TERT protein
Proteasome Inhibitors
Proteasome Endopeptidase Complex
Immunoprecipitation
Doxorubicin
Lysine
Arginine
Apoptosis
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Oh, W. ; Lee, E. W. ; Lee, D. ; Yang, M. R. ; Ko, A. ; Yoon, C. H. ; Lee, H. W. ; Bae, Y. S. ; Choi, C. Y. ; Song, J. / Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT. In: Oncogene. 2010 ; Vol. 29, No. 28. pp. 4101-4112.
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Oh, W, Lee, EW, Lee, D, Yang, MR, Ko, A, Yoon, CH, Lee, HW, Bae, YS, Choi, CY & Song, J 2010, 'Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT', Oncogene, vol. 29, no. 28, pp. 4101-4112. https://doi.org/10.1038/onc.2010.160

Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT. / Oh, W.; Lee, E. W.; Lee, D.; Yang, M. R.; Ko, A.; Yoon, C. H.; Lee, H. W.; Bae, Y. S.; Choi, C. Y.; Song, J.

In: Oncogene, Vol. 29, No. 28, 01.07.2010, p. 4101-4112.

Research output: Contribution to journalArticle

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AU - Lee, E. W.

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AU - Ko, A.

AU - Yoon, C. H.

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AU - Song, J.

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