P21WAF1 modulates NF-κB signaling and induces anti-apoptotic protein Bcl-2 in Tax-expressing rat fibroblast
P21WAF1 modulates NF-κB signaling and induces anti-apoptotic protein Bcl-2 in Tax-expressing rat fibroblast
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DOI：
10.1016/j.virol.2004.11.023
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发表时间：
2005-02-05
期刊：
影响因子：
3.7
通讯作者：
Shimotohno, K
中科院分区：
文献类型：
--
作者：
Akita, K;Kawata, S;Shimotohno, K
在由人T细胞白血病病毒1型（HTI.V-1）Tax调控的细胞周期相关基因中，细胞周期蛋白依赖性激酶（CDK）抑制剂p21（WAF 1）在HTLV-1感染的细胞中上调。以前，我们报道p21（WAF 1）刺激Tax依赖性NF-κ B活化，影响各种细胞过程，包括增殖，分化和凋亡。在HTLV-1感染的细胞中，Tax主要参与NF-κ B信号传导的组成性激活。在这里，我们证明p21（WAF 1）通过诱导p100/52（一种NF-κ B相关蛋白）影响Tax依赖性NF-κ B信号传导。Tax转化的大鼠成纤维细胞系W 4表现出NF-κ B信号传导的组成性激活，可能由RelB的过表达介导。由于p21（WAFI）启动子的甲基化而缺乏内源性表达的W 4细胞中p21（WAFI）的异位表达诱导p100/52的表达。Bcl-2的表达也上调异位p21（WAFI）在这个细胞系中，这表明，p21（WAFI）通过调节NF-κ B信号转导在Tax表达大鼠成纤维细胞的凋亡调控中起着重要的作用。我们还解决了在HTLV-1感染的细胞中NF-κ B相关蛋白的表达。(C)2004年爱思唯尔公司All rights reserved.
Of the cell cycle-associated genes regulated by human T-cell leukemia virus type-1 (HTI.V-1) Tax, cyclin-dependent kinase (CDK) inhibitor p21(WAF1) is upregulated in HTLV-1-infected cells. Previously, we reported that p21(WAF1) stimulated Tax-dependent NF-kappaB activation which influences a variety of cellular processes, including proliferation, differentiation, and apoptosis. In HTLV-1-infected cells, Tax is primarily involved in the constitutive activation of NF-kappaB signaling. Here, we demonstrate that p21(WAF1) affects Tax-dependent NF-kappaB signaling by inducing p 100/52, an NF-kappaB-related protein. W4, a Tax-transformed rat fibroblast cell line, exhibits the constitutive activation of NF-kappaB signaling, potentially mediated by overexpression of RelB. Ectopic expression of p21(WAF1) in W4 cells, which lack endogenous expression due to methylation of the p21(WAFI) promoter, induces the expression of p 100/52. Bcl-2 expression was also upregulated by ectopic p21(WAF1) in this cell line, suggesting that p21(WAFI) plays an important role in the regulation of apoptosis by modulating NF-kappaB signaling in Tax-expressing rat fibroblasts. We also address the expression of NF-kappaB-related proteins in HTLV-1 -infected cells. (C) 2004 Elsevier Inc. All rights reserved.