Nuclear Factor-κB p65 Mediates Tumor Necrosis Factor α-induced Nuclear Translocation of Telomerase Reverse Transcriptase Protein

Abstract Sustained proliferation of cancer cells requires telomerase to maintaintelomeres that regulate chromosomal stability and cellular mitosis. Ex-pression of human telomerase reverse transcriptase (hTERT) catalyticsubunit, which modulates telomerase activity, is regulated at both thetranscriptional level and via phosphorylation by Akt kinase. Moreover,nuclear localization of hTERT is required to promote elongation of te-lomere sequences. In this study, we show for the first time that hTERTprotein interacts directly with nuclear factor (NF)- B p65 in MM.1S cells.Importantly, tumor necrosis factor (TNF ) modulates telomerase ac-tivity by inducing translocation from the cytoplasm to the nucleus ofhTERT protein bound to NF- B p65. Conversely, a specific I B kinase(IKK) inhibitor PS-1145, and a specific NF- B nuclear translocationinhibitor SN-50, both block TNF -induced hTERT nuclear translocation.These studies suggest that NF- B p65 plays a pivotal role in regulatingtelomerase by modulating its nuclear translocation.

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