Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 316, Issue 2, Pages 528-532Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.02.080
Keywords
telomerase; hTERT; nuclear translocation; TNF alpha; NF-kappa B; Akt
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Funding
- PHS HHS [R0-1 50947, P0-1 78378] Funding Source: Medline
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Maintenance of telomeres regulates chromosomal stability and cellular mitosis through a checkpoint mechanism. Continuous cell proliferation requires telomerase to maintain chromosomal stability and to counteract the cellular mitotic clock. Importantly, nuclear expression of telomerase activity is required for elongation of telomere sequences. In this study, we show that tumor necrosis factor alpha (TNFalpha) induces telomerase activity in the cytoplasm of peripheral blood lymphocytes (PBL) at 60 min, followed by translocation of activated telomerase to the nucleus at 120 min. Conversely, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin blocks TNFalpha-induced activation of telomerase, whereas the specific NF-kappaB translocation inhibitor SN-50 blocks TNFalpha-induced nuclear translocation of activated telomerase. These studies suggest that activation and nuclear translocation of telomerase are regulated by PI3K/Akt/NF-kappaB signaling pathways in PBL. (C) 2004 Elsevier Inc. All rights reserved.
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