HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX INDUCES EXPRESSION OF THE REL-RELATED FAMILY OF KAPPA-B ENHANCER-BINDING PROTEINS - EVIDENCE FOR A PRETRANSLATIONAL COMPONENT OF REGULATION
HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX INDUCES EXPRESSION OF THE REL-RELATED FAMILY OF KAPPA-B ENHANCER-BINDING PROTEINS - EVIDENCE FOR A PRETRANSLATIONAL COMPONENT OF REGULATION
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DOI：
10.1128/jvi.65.12.6892-6899.1991
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发表时间：
1991-12-01
影响因子：
5.4
通讯作者：
GREENE, WC
中科院分区：
文献类型：
--
作者：
ARIMA, N;MOLITOR, JA;GREENE, WC
人T细胞白血病病毒I型（HTLV-I）的Tax蛋白作为其自身长末端重复序列以及选择细胞基因（包括白细胞介素-2和白细胞介素-2受体的α亚基）的有效转录激活因子。 这两个生长相关基因的Tax激活似乎涉及DNA结合蛋白的诱导核表达，所述DNA结合蛋白特异性地接合存在于这些基因的5'调控区中的相关kappa-B增强子元件。 在人类T细胞中，kappa-B增强子结合活性已被识别为UV交联核蛋白加合物的意外大家族，称为p50，p55，p75和p85。 这些DNA-蛋白质加合物中的每一种的蛋白质组分已被证明与v-rel癌基因产物具有结构相似性。 p55加合物由源自105-kDa前体多肽的NF-κ-B的50-kDa亚基组成，而p50加合物含有与NF-κ-B p50密切相关的较小蛋白质。 p75加合物含有NF-κ-B的65-kDa亚基，而p85加合物由人c-rel原癌基因产物组成。 我们现在证明，在没有其他病毒pX基因产物的情况下，HTLV-1 Tax能够诱导人T细胞中所有四种κ-B结合蛋白的核表达，其中最显著的作用涉及c-Rel和NF-κ-B p65。 Tax诱导的c-Rel和NF-κ-B p50的核表达至少部分在翻译前水平受到调节，涉及c-Rel和NF-κ-B p105 mRNA表达的增加。 为了研究这些κ-B特异性蛋白质在被整个HTLV-I感染的细胞中的表达模式，从成人T细胞白血病患者的外周血建立了7个克隆的HTLV-I感染的T细胞系。 值得注意的是，这七个细胞系中只有三个产生Tax，并且c-rel mRNA和核蛋白表达仅限于这三个细胞系。 相反，NF-κ-B p50和NF-κ-B p65在所有7种HTLV-1感染的细胞系的细胞核中组成型表达，即使在没有可检测的Tax或其他病毒基因表达的情况下。 这些发现提高了HTLV-1感染后NF-κ-B p50和NF-κ-B p65诱导的核表达的替代的Tax非依赖性途径的可能性。
The Tax protein of the human T-cell leukemia virus type I (HTLV-I) serves as a potent transcriptional activator of its own long terminal repeat as well as select cellular genes, including interleukin-2 and the alpha subunit of the interleukin-2 receptor. Tax activation of these two growth-related genes appears to involve the induced nuclear expression of DNA-binding proteins that specifically engage related kappa-B enhancer elements present in the 5' regulatory regions of these genes. In human T cells, kappa-B enhancer-binding activity has been discerned as an unexpectedly large family of UV cross-linked nucleoprotein adducts, termed p50, p55, p75, and p85. The protein components of each of these DNA-protein adducts have been shown to share structural similarity with the v-rel oncogene product. The p55 adduct is composed of the 50-kDa subunit of NF-kappa-B derived from a 105-kDa precursor polypeptide, while the p50 adduct contains a smaller protein that is closely related to NF-kappa-B p50. The p75 adduct contains the 65-kDa subunit of NF-kappa-B, while the p85 adduct is composed of the human c-rel proto-oncogene product. We now demonstrate that HTLV-I Tax, in the absence of other viral pX gene products, is capable of inducing the nuclear expression of all four of these kappa-B-binding proteins in human T cells, with most marked effects involving c-Rel and NF-kappa-B p65. Tax induction of the nuclear expression of c-Rel and NF-kappa-B p50 is regulated, at least in part, at a pretranslational level involving increases in c-rel and NF-kappa-B p105 mRNA expression. To study the pattern of expression of these kappa-B-specific proteins in cells infected with the whole HTLV-I, seven cloned HTLV-I-infected T-cell lines were established from the peripheral blood of patients with adult T-cell leukemia. Of note, only three of these seven cell lines produced Tax, and c-rel mRNA and nuclear protein expression was confined to these three cell lines. In contrast, NF-kappa-B p50 and NF-kappa-B p65 were constitutively expressed in the nuclei of all seven of the HTLV-I-infected cell lines, even in the absence of detectable Tax or other viral gene expression. These findings raise the possibility of an alternate, Tax-independent pathway for the induced nuclear expression of NF-kappa-B p50 and NF-kappa-B p65 following HTLV-I infection.