TAX PROTEIN OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I BINDS TO THE ANKYRIN MOTIFS OF INHIBITORY FACTOR KAPPA-B AND INDUCES NUCLEAR TRANSLOCATION OF TRANSCRIPTION FACTOR NF-KAPPA-B PROTEINS FOR TRANSCRIPTIONAL ACTIVATION
TAX PROTEIN OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I BINDS TO THE ANKYRIN MOTIFS OF INHIBITORY FACTOR KAPPA-B AND INDUCES NUCLEAR TRANSLOCATION OF TRANSCRIPTION FACTOR NF-KAPPA-B PROTEINS FOR TRANSCRIPTIONAL ACTIVATION
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DOI：
10.1073/pnas.91.9.3584
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
YOSHIDA, M
中科院分区：
文献类型：
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作者：
HIRAI, H;SUZUKI, T;YOSHIDA, M
人类 T 细胞白血病病毒 I 型引起成人 T 细胞白血病和热带痉挛性截瘫，其调节蛋白 Tax 与人类 T 细胞白血病病毒 I 型的致病活性有关。Tax 通过特定增强子激活病毒和细胞基因的转录：人类 T 细胞白血病病毒 I 型的 21 bp 增强子、白细胞介素 2 的核因子 kappa B (NF-kappa B) 结合位点受体α基因和c-fos的血清反应元件。 Tax 与增强子结合蛋白结合，包括 cAMP 反应元件结合蛋白、cAMP 反应元件调节剂、转录因子 NF-kappa B p50 和 p67(SRF)，并与每个增强子 DNA 间接结合。除了这种机制之外，我们在此报告了 Tax 与抑制因子 kappa B gamma (I-kappa B) gamma 结合，后者与 NF-kappa B 蛋白异二聚体 p50-p65 或同二聚体 p50-p50 形成复合物，并将其保留在细胞质中。 Tax 与 I-kappa B gamma 结合可诱导 NF-kappa B p65 的核转位。与 p65 的这种核易位相关，由 kappa B 增强子指导的转录被强烈激活。 Tax 与 I-kappa B gamma 的锚蛋白基序结合，表明它可能与许多其他携带锚蛋白蛾的蛋白质相互作用，从而促进各种调节过程。这是癌蛋白 Tax 转录激活的一种不同机制，并且似乎与通过间接结合增强子 DNA 的反式激活无关。
Human T-cell leukemia virus type I causes adult T-cell leukemia and tropical spastic paraparesis, and its regulator protein Tax has been implicated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through specific enhancers: the 21-bp enhancer of human T-cell leukemia virus type I, the nuclear factor kappa B (NF-kappa B)-binding site of the interleukin 2 receptor alpha gene, and the serum-responsive element of c-fos. Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67(SRF), and associates with each enhancer DNA indirectly. In addition to this mechanism, we report here that Tax binds to inhibitory factor kappa B gamma (I-kappa B) gamma, which forms a complex with NF-kappa B protein heterodimer p50-p65 or homodimer p50-p50 and retains them in the cytoplasm. Tax binding to I-kappa B gamma induces nuclear translocation of NF-kappa B p65. In association with this nuclear translocation of p65, transcription directed by the kappa B enhancer is strongly activated. Tax binds to the ankyrin motifs of I-kappa B gamma, suggesting its possible interaction with many other proteins carrying ankyrin moths contributing to various regulatory processes. This is a different mechanism of transcriptional activation by the oncoprotein Tax and seems to be independent from the trans-activation through indirect binding to enhancer DNAs.