Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine Joint Metastasis Research Society-AACR Conference on Metastasis
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[Cancer Research 63, 18-21, January 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Nuclear Factor-{kappa}B p65 Mediates Tumor Necrosis Factor {alpha}-induced Nuclear Translocation of Telomerase Reverse Transcriptase Protein1

Masaharu Akiyama, Teru Hideshima, Toshiaki Hayashi, Yu-Tzu Tai, Constantine S. Mitsiades, Nicholas Mitsiades, Dharminder Chauhan, Paul Richardson, Nikhil C. Munshi and Kenneth C. Anderson2

Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115 [M. A., T. Hi., T. Ha., Y-T. T., C. S. M., N. M., D. C., P. R., N. C. M., K. C. A.], and Veterans Administration Boston Healthcare System, West Roxbury, Massachusetts 02132 [N. C. M.]

Sustained proliferation of cancer cells requires telomerase to maintain telomeres that regulate chromosomal stability and cellular mitosis. Expression of human telomerase reverse transcriptase (hTERT) catalytic subunit, which modulates telomerase activity, is regulated at both the transcriptional level and via phosphorylation by Akt kinase. Moreover, nuclear localization of hTERT is required to promote elongation of telomere sequences. In this study, we show for the first time that hTERT protein interacts directly with nuclear factor (NF)-{kappa}B p65 in MM.1S cells. Importantly, tumor necrosis factor {alpha} (TNF{alpha}) modulates telomerase activity by inducing translocation from the cytoplasm to the nucleus of hTERT protein bound to NF-{kappa}B p65. Conversely, a specific I{kappa}B kinase (IKK) inhibitor PS-1145, and a specific NF-{kappa}B nuclear translocation inhibitor SN-50, both block TNF{alpha}-induced hTERT nuclear translocation. These studies suggest that NF-{kappa}B p65 plays a pivotal role in regulating telomerase by modulating its nuclear translocation.




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Copyright © 2003 by the American Association for Cancer Research.