HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Zhao, Tiejun; Wang, Zhilong; Fang, Jinyong; Cheng, Wenzhao; Zhang, Shujun; Huang, Jinhua; Xu, Lingling; Gou, Hongwei; Zeng, Ling‐Hui; Jin, Zhigang; Matsuoka, Masao

doi:10.1073/pnas.2115316119

Cited by 15 publications

(31 citation statements)

References 52 publications

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“…36 Moreover, we found that YAP could interact with Tax. 36 Thus we speculate whether YAP may have other critical roles in promoting leukemogenesis through association with Tax protein.…”

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confidence: 83%

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YAP suppresses human T‐cell leukemia virus type 1 transcription

Li,

Zou,

Zhang

et al. 2023

Journal of Medical Virology

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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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“…36 Moreover, we found that YAP could interact with Tax. 36 Thus we speculate whether YAP may have other critical roles in promoting leukemogenesis through association with Tax protein.…”

mentioning

confidence: 83%

“…36 NF-κB/p65-induced YAP activation was essential for maintaining the proliferation of ATL cells in vitro and in vivo. 36 Moreover, we found that YAP could interact with Tax. 36 Thus we speculate whether YAP may have other critical roles in promoting leukemogenesis through association with Tax protein.…”

mentioning

confidence: 97%

YAP suppresses human T‐cell leukemia virus type 1 transcription

Li,

Zou,

Zhang

et al. 2023

Journal of Medical Virology

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“…Tax and HBZ are currently acknowledged as two HTLV‐1 oncogenes with quite distinct mechanisms for oncogenesis. Tax is able to activate important cellular pathways including those responsible for T‐cell activation and expansion, 35 and is thereby considered a key player in HTLV‐1 persistence. Meanwhile, Tax appears to be a strong antigen that triggers cytotoxic T cell (CTL) response killing HTLV‐1 infected cells effectively.…”

Section: Tax and Hbzmentioning

confidence: 99%

HTLV‐1 persistent infection and ATLL oncogenesis

Zuo

Zhou

Yang

et al. 2022

Journal of Medical Virology

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Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus; whereas HTLV‐1 mainly persists in the infected host cell as a provirus, it also causes a malignancy called adult T‐cell leukemia/lymphoma (ATLL) in about 5% of infection. HTLV‐1 replication is in most cases silent in vivo and viral de novo infection rarely occurs; HTLV‐1 rather relies on clonal proliferation of infected T cells for viral propagation as it multiplies the number of the provirus copies. It is mechanistically elusive how leukemic clones emerge during the course of HTLV‐1 infection in vivo and eventually cause the onset of ATLL. This review summarizes our current understanding of HTLV‐1 persistence and oncogenesis, with the incorporation of recent cutting‐edge discoveries obtained by high‐throughput sequencing.

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“…Finally, the Hippo signal effector, YAP, known for its implication in the regulation of glutaminolysis, was found to be activated in ATL and its activation to be essential to maintain cellular proliferation of HTLV-1-infected cells. The activation was found to be induced via Tax protein through NF-κB [ 222 ].…”

Section: Metabolic Reprogramming In Oncovirusesmentioning

confidence: 99%

An Update on the Metabolic Landscape of Oncogenic Viruses

Gaballah

Bartosch

2022

Cancers

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Viruses play an important role in cancer development as about 12% of cancer types are linked to viral infections. Viruses that induce cellular transformation are known as oncoviruses. Although the mechanisms of viral oncogenesis differ between viruses, all oncogenic viruses share the ability to establish persistent chronic infections with no obvious symptoms for years. During these prolonged infections, oncogenic viruses manipulate cell signaling pathways that control cell cycle progression, apoptosis, inflammation, and metabolism. Importantly, it seems that most oncoviruses depend on these changes for their persistence and amplification. Metabolic changes induced by oncoviruses share many common features with cancer metabolism. Indeed, viruses, like proliferating cancer cells, require increased biosynthetic precursors for virion production, need to balance cellular redox homeostasis, and need to ensure host cell survival in a given tissue microenvironment. Thus, like for cancer cells, viral replication and persistence of infected cells frequently depend on metabolic changes. Here, we draw parallels between metabolic changes observed in cancers or induced by oncoviruses, with a focus on pathways involved in the regulation of glucose, lipid, and amino acids. We describe whether and how oncoviruses depend on metabolic changes, with the perspective of targeting them for antiviral and onco-therapeutic approaches in the context of viral infections.

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HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Cited by 15 publications

References 52 publications

YAP suppresses human T‐cell leukemia virus type 1 transcription

YAP suppresses human T‐cell leukemia virus type 1 transcription

HTLV‐1 persistent infection and ATLL oncogenesis

An Update on the Metabolic Landscape of Oncogenic Viruses

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