TNFα induces rapid activation and nuclear translocation of telomerase in human lymphocytes
TNFα induces rapid activation and nuclear translocation of telomerase in human lymphocytes
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DOI：
10.1016/j.bbrc.2004.02.080
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发表时间：
2004-04-02
影响因子：
3.1
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Akiyama, M;Yamada, O;Anderson, KC
端粒的维持通过检查点机制调节染色体的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的稳定性，并抵消细胞有丝分裂的时钟。重要的是，端粒酶活性的核表达是端粒序列延长所必需的。在这项研究中，我们发现肿瘤坏死因子α(TNFα)在60min时诱导外周血淋巴细胞(PBL)胞浆中的端粒酶活性，随后在120min时激活的端粒酶转位到细胞核。相反，磷酸肌醇3-激酶(PI3K)抑制剂Wortmannin可阻断TNFpha诱导的端粒酶激活，而特异性的NF-kappaB转位抑制剂SN-50则可阻断TNFpha诱导的激活的端粒酶的核转位。这些研究表明，PBL中端粒酶的激活和核转位受PI3K/Akt/NF-kappaB信号通路的调控。(C)2004 Elsevier Inc.保留所有权利。
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.