Direct inhibition of RNAse T2 expression by the HTLV-1 viral protein Tax.
Direct inhibition of RNAse T2 expression by the HTLV-1 viral protein Tax.
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DOI：
10.3390/v3081485
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Lemasson I
中科院分区：
文献类型：
--
作者：
Polakowski N;Han H;Lemasson I
成人T细胞白血病（ATL）是由人类T细胞白血病病毒1型（HTLV-1）感染引起的主要疾病之一。病毒编码的Tax蛋白被认为是引发这种疾病发展的早期事件，因为它能够促进T细胞的永生化和其他细胞类型的转化。这些过程可以通过病毒蛋白通过与许多转录调节因子的相互作用直接解除特定细胞基因表达的能力来辅助。为了确定Tax定位的基因启动子，我们通过染色质免疫沉淀（ChIP）试验从HTLV-1感染的T细胞系中分离Tax-DNA复合物，并使用DNA探测CpG岛微阵列。发现RNASET 2基因内的一个位点被Tax占据。实时PCR分析证实了这一结果，并且Tax在未感染细胞中的瞬时表达导致病毒蛋白募集到启动子。该事件与RNase T2 mRNA和蛋白水平的降低相关，表明Tax抑制该基因的表达。RNase T2表达的缺失发生在某些血液恶性肿瘤和其他形式的癌症中，并且RNase T2最近被报道作为肿瘤抑制剂起作用。因此，通过税收降低RNase T2水平可能在ATL发展中发挥作用。
Adult T-cell leukemia (ATL) is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1) infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP) assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.
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