Akiyama Masaharu, Yamada Osamu, Hideshima Teru, Yanagisawa Takaaki, Yokoi Kentaro, Fujisawa Kohji, Eto Yoshikatsu, Yamada Hisashi, Anderson Kenneth C
Department of Pediatrics, Jikei University School of Medicine, Tokyo 105-8461, Japan.
Biochem Biophys Res Commun. 2004 Apr 2;316(2):528-32. doi: 10.1016/j.bbrc.2004.02.080.
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.
端粒的维持通过一种检查点机制调节染色体稳定性和细胞有丝分裂。持续的细胞增殖需要端粒酶来维持染色体稳定性并抵消细胞有丝分裂时钟。重要的是，端粒酶活性的核表达是端粒序列延长所必需的。在本研究中，我们发现肿瘤坏死因子α（TNFα）在60分钟时诱导外周血淋巴细胞（PBL）细胞质中的端粒酶活性，随后在120分钟时活化的端粒酶转运至细胞核。相反，磷酸肌醇3激酶（PI3K）抑制剂渥曼青霉素可阻断TNFα诱导的端粒酶活化，而特异性NF-κB转运抑制剂SN-50可阻断TNFα诱导的活化端粒酶的核转运。这些研究表明，PBL中端粒酶的活化和核转运受PI3K/Akt/NF-κB信号通路调控。
