YAP suppresses human T-cell leukemia virus type 1 transcription.
Hengbo LiFeng ZouJie ZhangShengyu ZhuKaifei ChuXu ZhangTiejun ZhaoPublished in: Journal of medical virology (2023)
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.
Keyphrases
- transcription factor
- gene expression
- induced apoptosis
- endothelial cells
- bone marrow
- sars cov
- acute myeloid leukemia
- dna methylation
- oxidative stress
- binding protein
- signaling pathway
- poor prognosis
- young adults
- immune response
- protein protein
- cell proliferation
- amino acid
- drug delivery
- diffuse large b cell lymphoma
- induced pluripotent stem cells
- heat shock
- pi k akt