Dataset Information

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-?B signaling.

ABSTRACT: Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-?B (NF-?B) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-?B binding site in the EGR1 promotor or inhibition of NF-?B activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-?B induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-?B pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-?B activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-?B activation in HTLV-1-infected and Tax-expressing cells. Both NF-?B activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-?B activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

SUBMITTER: Huang Q

PROVIDER: S-EPMC5584236 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Huang Qingsong Q Niu Zhiguo Z Han Jingxian J Liu Xihong X Lv Zhuangwei Z Li Huanhuan H Yuan Lixiang L Li Xiangping X Sun Shuming S Wang Hui H Huang Xinxiang X

Oncotarget 20170508 31

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibit ...[more]

PMID: 28881635

Similar Datasets

Project description:BackgroundRetroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway.ResultsThe comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1.ConclusionsBoth Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway.

Dataset Information

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-?B signaling.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets