长终端重复
逆转录病毒
抄写(语言学)
生物
病毒学
人嗜T淋巴细胞病毒1型
转录因子
白血病
心理压抑
效应器
细胞生物学
分子生物学
病毒
基因
T细胞白血病
基因表达
遗传学
语言学
哲学
作者
Hengbo Li,Feng Zhang,Jie Zhang,Shengyu Zhu,Kaifei Chu,Xu Zhou,Tiejun Zhao
摘要
Abstract Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus that causes adult T‐cell leukemia/lymphoma (ATL). HTLV‐1 encodes Tax protein that activates transcription from viral long terminal repeats (LTR). Multiple cofactors are involved in the regulation of HTLV‐1 transcription via association with Tax. Yes‐associated protein (YAP), which is the key effector of Hippo pathway, is elevated and activated in ATL cells. In this study, we reported that YAP protein suppressed Tax activation of HTLV‐1 5′ LTR but not 3′ LTR. The activation of the 5′ LTR by Tax was potentiated when YAP was depleted. Moreover, overexpression of YAP repressed HTLV‐1 plus‐strand viral gene expression and virion production, whereas compromising YAP by RNA inference augmented the expression of HTLV‐1 protein. As mechanisms of YAP‐mediated viral transcription inhibition, we found that YAP interacted with Tax, and prevented the association between Tax and p300. It finally led to the inhibition of recruitment of Tax to the Tax‐responsive element in the 5′ LTR of HTLV‐1. Taken together, our results demonstrate the negative regulatory function of YAP in Tax activation of HTLV‐1 transcription. It may achieve sufficient transcriptional repression to maintain persistent infection and long‐term latency of HTLV‐1 in the host cells.
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