Both Rbx1 and Rbx2 exhibit a functional role in the HIV-1 Vif-Cullin5 E3 ligase complex in vitro

Wang, Xiaodan; Wang, Xiaoying; Wang, Weiran; Zhang, Jingyao; Wang, Jiawen; Wang, Chu; Lv, Mingyu; Zuo, Tao; Liu, Donglai; Zhang, Haihong; Wu, Jiaxin; Yu, Bin; Kong, Wei; Wu, Hui; Yu, Xianghui

doi:10.1016/j.bbrc.2015.04.077

Cited by 14 publications

(8 citation statements)

References 26 publications

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“…Moreover, it has been shown that immune inhibitory molecules, including LAG-3 [ 54 ] and CD160 [ 55 ], have higher levels in CPs than in LTNPs and UCs and are involved in immune exhaustion that accelerated HIV-1 disease progression. Additionally, we also identified 184 unique DEGs in LTNPs, which were involved in HIV/AIDS disease control or progression, including 38 up-regulated genes such as CCL22 (a soluble HIV-suppressive factor [ 56 ], LILRB3 (related to immune protection for HIV-1 infection) [ 57 ] and CCL7/MCP-3 (competed for HIV-1 gp120 binding) [ 58 ], and 146 down-regulated genes such as TMPO (involved in HIV-1 Tat-induced apoptosis of T cells) [ 59 ], BST2 (increased in SIV-infected rhesus monkeys) [ 60 ], RBX1 (involved in proteasomal degradation of APOBEC3G) [ 61 ], CCNA2 (contributed to loss of SAMHD1 ability to inhibit HIV-1) [ 62 ] and some unreported genes such as FOXM1, EZH2 and PAFF1 (Additional file 2 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

et al. 2017

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BackgroundHIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7–10 years, but keeping high CD4+ T cell counts and low viral load in the absence of antiretroviral treatment, while loss of CD4+ T cells and high viral load were observed in the most of HIV-1-infected individuals with chronic progressors (CPs) However, the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved.MethodsTo identify microRNAs (miRNAs) and their target genes related to distinct clinical outcomes in HIV-1 infection, we performed the integrative transcriptome analyses in two series GSE24022 and GSE6740 by GEO2R, R, TargetScan, miRDB, and Cytoscape softwares. The functional pathways of these differentially expressed miRNAs (DEMs) targeting genes were further analyzed with DAVID.ResultsWe identified that 7 and 19 DEMs in CD4+ T cells of LTNPs and CPs, respectively, compared with uninfected controls (UCs), but only miR-630 was higher in CPs than that in LTNPs. Further, 478 and 799 differentially expressed genes (DEGs) were identified in the group of LTNPs and CPs, respectively, compared with UCs. Compared to CPs, four hundred and twenty-four DEGs were identified in LTNPs. Functional pathway analyses revealed that a close connection with miRNA-mRNA in HIV-1 infection that DEGs were involved in response to virus and immune system process, and RIG-I-like receptor signaling pathway, whose DEMs or DEGs will be novel biomarkers for prediction of clinical outcomes and therapeutic targets for HIV-1.ConclusionsIntegrative transcriptome analyses showed that distinct transcriptional profiles in CD4+ T cells are associated with different clinical outcomes during HIV-1 infection, and we identified a circulating miR-630 with potential to predict disease progression, which is necessary to further confirm our findings in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1130-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

et al. 2017

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“…PCR fragments encoding hnRNP A1 or SPSB1 with truncations, deletions or point mutations were made by a two-step PCR using primers listed in the Supplementary information, Table S4. pST39-Rbx2-His-Cullin5 and pST39-ElonginB-CBFbeta-Elong-inC-Vif-His were kindly provided by Dr. Xianghui Yu (Jilin University, Changchun, China) [60]. To generate pST39-Elong-inB-ElonginC, CBFbeta and Vif-His sequences were removed from pST39-ElonginB-CBFbeta-ElonginC-vif-His.…”

Section: Plasmid Constructionmentioning

confidence: 99%

SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling

Wang

Chen

et al. 2017

Cell Res

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Extracellular signals have been shown to impact on alternative pre-mRNA splicing; however, the molecular mechanisms and biological significance of signal-induced splicing regulation remain largely unknown. Here, we report that epidermal growth factor (EGF) induces splicing changes through ubiquitylation of a well-known splicing regulator, hnRNP A1. EGF signaling upregulates an E3 ubiquitin (Ub) ligase adaptor, SPRY domain-containing SOCS box protein 1 (SPSB1), which recruits Elongin B/C-Cullin complexes to conjugate lysine 29-linked polyUb chains onto hnRNP A1. Importantly, SPSB1 and ubiquitylation of hnRNP A1 have a critical role in EGF-driven cell migration. Mechanistically, EGF-induced ubiquitylation of hnRNP A1 together with the activation of SR protein kinases (SRPKs) results in the upregulation of a Rac1 splicing isoform, Rac1b, to promote cell motility. These findings unravel a novel crosstalk between protein ubiquitylation and alternative splicing in EGF/EGF receptor signaling, and identify a new EGF/SPSB1/hnRNP A1/Rac1 axis in modulating cell migration, which may have important implications for cancer treatment.

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“…Binding of Elongin B/C changes the conformation of Vif, facilitating its interaction with CBF-β and Cul5 [ 211 ]. Although both Rbx1 and Rbx2 can interact with Cul5, only the knockdown of Rbx2, but not that of Rbx1, impairs Vif-induced A3G degradation [ 212 ].…”

Section: Virus-related Cul5-containing Ubiquitin Ligasesmentioning

confidence: 99%

The role of cullin 5-containing ubiquitin ligases

et al. 2016

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The suppressor of cytokine signaling (SOCS) box consists of the BC box and the cullin 5 (Cul5) box, which interact with Elongin BC and Cul5, respectively. SOCS box-containing proteins have ubiquitin ligase activity mediated by the formation of a complex with the scaffold protein Cul5 and the RING domain protein Rbx2, and are thereby members of the cullin RING ligase superfamily. Cul5-type ubiquitin ligases have a variety of substrates that are targeted for polyubiquitination and proteasomal degradation. Here, we review the current knowledge on the identification of Cul5 and the regulation of its expression, as well as the signaling pathways regulated by Cul5 and how viruses highjack the Cul5 system to overcome antiviral responses. Identification and regulation of cullin 5Cullin 5 (Cul5) was originally identified as a vasopressin-activated calcium-mobilizing (VACM-1) protein, an arginine vasopressin (AVP) receptor [1]. AVP is a nonapeptide that regulates body fluid and blood pressure homeostasis. VACM-1 is recognized as Cul5 because of its homology to the Caenorhabditis elegans gene Cul5 [2,3]. Cul5 is expressed in many cells and organs, including endothelial cells, brain, kidney collecting tubule cells, and vascular endothelial cells [2,[4][5][6]7]. Cul5 inhibits cyclic AMP production, and this effect is reversed by staurosporin, a protein kinase A (PKA) inhibitor, or by mutating S730A, the PKA-dependent phosphorylation site in the Cul5 sequence in COS-1 cells [8]. The inhibitory effect of Cul5 on AVP-stimulated cAMP production is enhanced by a protein kinase C inhibitor [8]. CUL-5 expression is downregulated in 82 % (41/50) of breast tumors compared with matched normal tissues [9]. Overexpression of Cul5 in T47D breast cancer cells decreases cell growth and mitogen activated protein kinase (MAPK) phosphorylation [10], and Cul5 overexpression downregulates early growth response 1 (EGR-1) protein expression and upregulates Fas-L mRNA expression [10]. The regulation of both MAPK and EGR-1 pathways by 17β-estradiol led to the examination of estrogen-dependent T47D cell growth, which showed that Cul5 inhibits basal and 17β-estradiol-dependent cell growth and MAPK phosphorylation [11].Resveratrol (trans-3,5,4′-trihydroxystilbene), which inhibits tumor initiation and promotion, is a natural component of the human diet, and its wide range of biological activities has been demonstrated in vivo and in vitro [12][13][14][15]. The antiproliferative effect of resveratrol is significantly enhanced by Cul5 overexpression in T47D cells [16].The expression of Cul5 is regulated by several stimuli and pathways (Fig. 1). Resveratrol upregulates Cul5 expression and decreases T47D cell growth, suggesting that the antiproliferative effect of resveratrol is mediated by Cul5 [16]. Cul5 is a flexible scaffold protein with a preferred distribution of conformational states [17], and NEDD8 modification (neddylation) alters the conformation of Cul5 and activates it [18]. Cul5(S730A) accelerates cellular proliferation and induces an...

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Both Rbx1 and Rbx2 exhibit a functional role in the HIV-1 Vif-Cullin5 E3 ligase complex in vitro

Cited by 14 publications

References 26 publications

Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling

The role of cullin 5-containing ubiquitin ligases

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