XBP-1, a Novel Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Binding Protein, Activates HTLV-1 Basal and Tax-Activated Transcription

Ku, Sebastian C. Y.; Lee, Jialing; Lau, Joanne; Gurumurthy, Meera; Ng, Raymond W. M.; Lwa, Siew Hui; Lee, Joseph; Klase, Zachary; Kashanchi, Fatah; Chao, Sheng-Hao

doi:10.1128/jvi.02054-07

Cited by 23 publications

(31 citation statements)

References 55 publications

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“…Other, less characterized, points of interaction by the AHR include Irf8, Xbp1, and Myc, which have been identified as potential direct transcriptional targets of the AHR in B cells using ChIP-on-chip and time course microarray analysis (De Abrew et al , 2010). Irf8 transcriptionally activates Bcl6 (Lee et al , 2006; Ku et al , 2008) and Xbp1 transcriptionally upregulates Tax1 (Ku et al , 2008) which, in turn, physically interacts with Bcl6 to enhance its repressive activity (Dean et al , 2009). Myc has been predicted to transcriptionally regulate Irf4 (Chen et al , 2007), which is a transcriptional activator of Prdm1 (Calame, 2008).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Abrew

Phadnis-Moghe

Crawford

et al. 2011

Toxicology and Applied Pharmacology

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Exposure to the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), alters B cell differentiation and suppresses antibody production. Previous genomic studies in mouse B cells identified Bach2 as a direct target of the AHR. Bach2 is known to repress expression of Prdm1, a key transcription factor involved in B cell differentiation, by binding to Maf elements (MAREs) in the regulatory regions of the gene. Chromatin immunopreciptiation followed by quantitative PCR in TCDD-treated lipopolysaccharide (LPS)-activated B cells showed increased binding of the AHR within the first intron in the Bach2 gene. The binding was further confirmed by electrophoretic mobility shift assay (EMSA). TCDD also induced expression of Bach2 in activated as well as resting B cells from 2 to 24 h post-treatment in a time and concentration-dependent manner. Expression of Prdm1 was decreased by TCDD at 24 h and was consistent with repression by Bach2. Increased DNA binding activity to the intron 5 MARE with increasing TCDD concentration was observed by EMSA. Supershifts identified the presence of Bach2 in the DNA binding complex associated with the intron5 MARE of Prdm1. Functional validation of the role of Bach2 in the suppression of B-cell differentiation by TCDD was performed using RNAi. Knockdown of Bach2 showed approximately 40% reversal in the TCDD-induced suppression of IgM secretion when compared to controls. The results suggest that the transcriptional regulation of Bach2 by the AHR is one of the mechanisms involved in the suppression of B-cell differentiation by TCDD.

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Section: Discussionmentioning

confidence: 99%

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Abrew

Phadnis-Moghe

Crawford

et al. 2011

Toxicology and Applied Pharmacology

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“…This approach generates an unspliceable version of the transcript (i.e., cXBP-1U) and is similar to that which was previously described. 16,25 The open reading frame for XBP-1U was similarly cloned to generate the plasmid CMV-cXBP-1U. The full-length cDNA sequence of Chinese hamster XBP-1 has been submitted to GenBank with the accession number FJ499339.…”

Section: Plasmid Constructionmentioning

confidence: 99%

“…Approximate conversion of IU to pg has been described previously. 25 For MAb ELISA, 96 well plates were pre-coated with 10 lg/mL of a goat anti-human IgG, IgA, and IgM antibody (SPD Scientific) and blocked in phosphate buffered saline containing 3% bovine serum albumin. The plate was then incubated with diluted samples of supernatant.…”

Section: Elisa and Western Blottingmentioning

confidence: 99%

Regulation of XBP‐1 signaling during transient and stable recombinant protein production in CHO cells

Toh

Lee

et al. 2009

Biotechnology Progress

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X-box binding protein 1 (XBP-1) is a key regulator of cellular unfolded protein response (UPR). The spliced isoform of XBP-1, XBP-1S, is a transcription activator, which is expressed only when UPR is induced. However, the impact of recombinant protein production on the regulation of XBP-1 signaling in CHO cells is not well understood. In this report, we cloned the Chinese hamster XBP-1 homolog to aid the investigation of the interplay between protein productivity, culture conditions, and endogenous XBP-1 signaling in CHO cells. Interestingly, expression of XBP-1S is detected in the non-producing and unstressed CHO-K1 cells. Transient expression of recombinant erythropoietin reveals a positive correlation between XBP-1 mRNA abundance and protein production level. However, such a correlation is not observed in batch cultivation of stable producing cell lines. The increased XBP-1 splicing is detected in late-phase cultures, suggesting that induction of XBP-1S may be a result of nutrient limitations or other environmental stresses rather than that of increased intracellular accumulation of recombinant proteins. Our data suggest that XBP-1 is a key determinant for the secretory capacity of CHO cells. Understanding its dynamic regulation hence provides a rational basis for cellular engineering strategies to improve recombinant protein secretion.

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“…XBP-1 is part of the ER stress response pathway, and alteration of its splicing has been shown to assist viruses establish persistent infections and promote the viral life cycle [19; 20; 21]. In this study, we examined the effect of the high-risk HPV-16 E5 protein on XBP-1 splicing.…”

Section: Introductionmentioning

confidence: 99%

The HPV-16 E5 protein represses expression of stress pathway genes XBP-1 and COX-2 in genital keratinocytes

Sudarshan

Schlegel

2010

Biochemical and Biophysical Research Communications

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The HPV-16 E5 protein resides in membranes of the endoplasmic reticulum (ER) and modulates cell growth and viral replication. In order to help define its biological activities, we analyzed E5-induced changes in human keratinocyte gene expression. Our studies identified the downregulation of spliced XBP-1 transcripts, a key player in the ER stress response, as a biochemical marker of E5 expression. IRE1α, the endoribonuclease responsible for XBP-1 RNA splicing, was also downregulated. Furthermore, cDNA microarray analysis revealed the repression of COX-2, another member of the ER stress pathway. In contrast, these genes were not altered either by the low-risk HPV-6b E5, or a C-terminal HPV-16 E5 mutant, in which the histidine and alanine residues (conserved in high-risk HPVs) were replaced with tyrosine and isoleucine (conserved in low-risk HPVs). HPV-16 E5 was also able to lower COX-2 mRNA levels in cells co-expressing E6/E7, suggesting that it might exert similar activity during viral replication. Interestingly, the E6/E7 genes were independently able to lower COX-2 transcripts compared to vector cells, indicating that multiple pathways of COX-2 repression exist. COX-2 downregulation by E5 could be overcome by thapsigargin or tunicamycin treatments, which initiate ER stress via calcium fluxes and abnormal protein glycosylation respectively, making it unlikely that E5 specifically tempers these pathways. Overall, our data indicate that E5 represses the cellular ER stress response and suggest a potential role for E5 during productive HPV infection.

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XBP-1, a Novel Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Binding Protein, Activates HTLV-1 Basal and Tax-Activated Transcription

Cited by 23 publications

References 55 publications

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Regulation of XBP‐1 signaling during transient and stable recombinant protein production in CHO cells

The HPV-16 E5 protein represses expression of stress pathway genes XBP-1 and COX-2 in genital keratinocytes

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