HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling

Huang, Qingsong; Niu, Zhiguo; Jing-xian, Han; Liu, Xihong; Lv, Zepeng; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

doi:10.18632/oncotarget.17699

Cited by 7 publications

(8 citation statements)

References 45 publications

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“…An additional mechanism that operates within the cells to maintain the NF-κB activation induced by Tax-1 is the positive feedback loop derived by NF-κB target genes. A recent report describes that the over-expression of the early growth response protein 1 (EGR1) induced by Tax-1 activation of NF-κB, results in the stabilization of EGR1 by direct interaction with Tax and nuclear translocation of p65, enhancing NF-κB activation (Huang et al, 2017 ). A similar positive loop is fostered by the overexpression of the interleukin receptor IL-17RB.…”

Section: Tax-mediated Nf-κb Activationmentioning

confidence: 99%

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

et al. 2018

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Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

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Section: Tax-mediated Nf-κb Activationmentioning

confidence: 99%

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

et al. 2018

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“…Unexpectedly, during our experiment, the expression level of egr1 in Hela cell line transfected with pCI-Tas increased about 3 times than that of the control (unpublished data). Egr1, a nuclear transcriptional regulator involved in the PKC signal pathway, was found to be associated with the HTLV-1Tax-responsive c/s-acting element [31]. Also, Egr1 was reported to be the direct target of the IGE-II gene which was induced by the PKC pathway during HCV pathogenesis and activated much more immune factors to defend foreign invasion of HCV [32].…”

Section: Discussionmentioning

confidence: 99%

The Regulation of Prototype Foamy Virus 5′Long Terminal Repeats and Internal Promoter by Endogenous Transcription Factors

et al. 2021

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Background: For foamy virus, the transactivator of spumaretrovirus (Tas) could bind directly to target DNA sequences termed as Tas responsive elements and trigger the viral internal promoter (IP) and long terminal repeat (LTR) promoters. The cellular endogenous factors also play an important role in viral gene expressions. We hypothesized that except the viral transcription factor Tas, the cellular endogenous factors also affect the viral gene expression. Methods: The full length of the prototype foamy virus (PFV) genome (U21247) was used to predict the potential binding sites of the transcription factors by online software JASPAR (http://jaspar.genereg.net) and Softberry (http://linux1.softberry.com/berry.phtml?topic=index&group=programs&subgroup=promoter). The Dual-Luciferase® Reporter Assay System (Promega, USA) was used to confirm the relative luciferase activities of the test groups. The different representative activating agents or inhibitors of each canonical signal pathway were used to identify the impact of these pathways on PFV 5′LTR and IP promoters. Results: The results showed different cellular endogenous factors might have respective effects on PFV 5′LTR and IP. It is worth mentioning that activator protein-1 and BCL2-associated athanogene 3, 2 kinds of vital proteins associated with NF-κB and PKC pathways, could activate the basal activity of 5′LTR and IP promoters but inhibit the Tas-regulated activity of both promoters. Furthermore, PFV Tas was identified to trigger the transcription of the NF-κB promoter. Conclusion: NF-κB had a negative effect on PFV 5′LTR and IP promoter activities, the PKC pathway might upregulate 5′LTR and IP promoter activities, and the JNK and NF-AT signal pathway could increase the Tas-regulated promoter activity of PFV 5′LTR. This study sheds light on the interaction between PFV and the host cell and may help utilize the viral promoters in retroviral vectors designed for gene transfer experiments.

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“…Further, the viral protein Tax was found to modulate cellular gene expression via CREB/ activating transcription factors (ATF)-, SRF-and NF-κBassociated pathways (Matsuoka and Jeang, 2007). More recent studies have shown that HTLV-1 infection, and Tax more specifically, upregulates EGR1 expression in infected T-cells (Huang et al, 2017). Moreover, using a luciferase reporter plasmid system, it was shown that both the SRE element and NF-κB binding sites within the EGR1 promoter are essential for regulating EGR1 transcription and Tax directly binds to the NF-κB binding site within the EGR1 promoter (Huang et al, 2017).…”

Section: Retroviridaementioning

confidence: 99%

Examining the role of EGR1 during viral infections

Lehman

Kehn-Hall

2022

Front. Microbiol.

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Early growth response 1 (EGR1) is a multifunctional mammalian transcription factor capable of both enhancing and/or inhibiting gene expression. EGR1 can be activated by a wide array of stimuli such as exposure to growth factors, cytokines, apoptosis, and various cellular stress states including viral infections by both DNA and RNA viruses. Following induction, EGR1 functions as a convergence point for numerous specialized signaling cascades and couples short-term extracellular signals to influence transcriptional regulation of genes required to initiate the appropriate biological response. The role of EGR1 has been extensively studied in both physiological and pathological conditions of the adult nervous system where it is readily expressed in various regions of the brain and is critical for neuronal plasticity and the formation of memories. In addition to its involvement in neuropsychiatric disorders, EGR1 has also been widely examined in the field of cancer where it plays paradoxical roles as a tumor suppressor gene or oncogene. EGR1 is also associated with multiple viral infections such as Venezuelan equine encephalitis virus (VEEV), Kaposi’s sarcoma-associated herpesvirus (KSHV), herpes simplex virus 1 (HSV-1), human polyomavirus JC virus (JCV), human immunodeficiency virus (HIV), and Epstein–Barr virus (EBV). In this review, we examine EGR1 and its role(s) during viral infections. First, we provide an overview of EGR1 in terms of its structure, other family members, and a brief overview of its roles in non-viral disease states. We also review upstream regulators of EGR1 and downstream factors impacted by EGR1. Then, we extensively examine EGR1 and its roles, both direct and indirect, in regulating replication of DNA and RNA viruses.

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HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling

Cited by 7 publications

References 45 publications

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

The Regulation of Prototype Foamy Virus 5′Long Terminal Repeats and Internal Promoter by Endogenous Transcription Factors

Examining the role of EGR1 during viral infections

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