Constitutive Activation of NF-κB in Primary Adult T-Cell Leukemia Cells
Constitutive Activation of NF-κB in Primary Adult T-Cell Leukemia Cells
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原代成体 T 细胞白血病细胞中 NF-κB 的组成型激活
DOI：
10.1182/blood.v93.7.2360.407k10_2360_2368
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发表时间：
1999
期刊：
影响因子：
20.3
通讯作者：
N. Yamamoto
中科院分区：
文献类型：
--
作者：
N. Mori;M. Fujii;S. Ikeda;Yasuaki Yamada;M. Tomonaga;D. Ballard;N. Yamamoto
人类T细胞白血病病毒I型（HTLV-1）是成人T细胞白血病（ATL）的病原体。病毒蛋白Tax诱导转录因子NF-κB的活化和核转位，NF-κB被认为在HTLV-I转化T细胞中起关键作用。然而，包括Tax在内的HTLV-I基因在ATL患者的原代白血病细胞中不显著表达。在这项研究中，我们研究了NF-κB活化的基础，在新鲜分离的白血病细胞从ATL患者。我们发现ATL患者的白血病细胞，像HTLV-1感染的T细胞系一样，显示组成型NF-κB DNA结合活性和IκB的降解增加（NF-κB的抑制剂）。尽管表达Tax的T细胞系中的NF-κB结合活性主要由p50/c-Rel组成，但新鲜ATL样品含有p50/p50和p50/p65异二聚体。一种来源于ATL白血病细胞的T细胞系TL-Om 1显示组成型NF-κB活性，以及IκB的降解增强，尽管缺乏可检测的Tax表达。有趣的是，TL-Om 1中的NF-κB由p50/p50和p50/p65组成，与新鲜原代白血病细胞中的NF-κ B相似。我们的研究结果表明，NF-κB的激活发生在ATL患者的白血病细胞通过Tax非依赖性机制，可能是由于不同的NF-κB亚基激活。
Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (ATL). The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-κB, which is proposed to play a crucial role in the transformation of T cells by HTLV-I. However, the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL patients. In this study, we examined the basis for NF-κB activation in freshly isolated leukemic cells from ATL patients. We found that leukemic cells from ATL patients, like HTLV-I–infected T-cell lines, display constitutive NF-κB DNA binding activity and increased degradation of IκB (an inhibitor of NF-κB). Whereas the NF-κB binding activity in Tax-expressing T-cell lines consisted mostly of p50/c-Rel, fresh ATL samples contained p50/p50 and p50/p65 heterodimers. One T-cell line derived from ATL leukemic cells, TL-Om1, displayed constitutive NF-κB activity, as well as enhanced degradation of IκB, despite the lack of detectable Tax expression. Interestingly, the NF-κB in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leukemic cells. Our results suggest that activation of NF-κB occurs through a Tax-independent mechanism in leukemic cells of ATL patients, possibly due to differential NF-κB subunit activation.
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DOI：
10.1073/pnas.87.24.10028
发表时间：
1990-12-01
影响因子：
11.1
作者：
MOLITOR, JA;WALKER, WH;GREENE, WC
通讯作者：
GREENE, WC
成人 T 细胞白血病中白细胞介素 10 基因的表达。
影响因子：
20.3
作者：
Mori,N;Gill,PS;Mougdil,T;Murakami,S;Eto,S;Prager,D
通讯作者：
Prager,D
影响因子：
8
作者：
J. Lanoix;J. Lacoste;N. Pépin;N. Rice;J. Hiscott
通讯作者：
J. Lanoix;J. Lacoste;N. Pépin;N. Rice;J. Hiscott
影响因子：
20.3
作者：
Mori, N;Prager, D
通讯作者：
Prager, D