The Bax Inhibitor-1 Gene Is Differentially Regulated in Adult Testis and Developing Lung by Two Alternative TATA-less Promoters

Jean, Jyh Chang; Oakes, Sean; Joyce-Brady, Martin

doi:10.1006/geno.1999.5761

Cited by 35 publications

(33 citation statements)

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“…11 It was shown that BI-1 is expressed in tissues in which the rate of apoptotic cell death is high such as in the lung during late prenatal and early postnatal development. 13 Furthermore, BI-1 is highly expressed in tumor cells such as human prostate cancer, human breast cancer, human brain tumor, or large cell lymphoma. 12,[14][15][16]30 In addition, in this work, we found BI-1 to be expressed in primary AML-blasts and -cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…11 BI-1 gene expression is accentuated not only in tissues with low apoptotic activity, such as the epithelium of the developing lung, but also in several human malignant tumors, such as prostate carcinoma, breast carcinoma, and brain tumors. [12][13][14][15] Grzmil et al 16 were able to increase spontaneous apoptosis rates in prostate carcinoma cell lines by suppressing BI-1 expression using specific small-interfering RNA. Lee et al 17 presented evidence that BI-1 regulates generation of reactive oxygen species in the context of endoplasmic reticulum stress and thus inhibits apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen

et al. 2009

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Using dendritic cells (DCs) electroporated with whole RNA isolated from blasts of a patient with acute myeloid leukemia (AML), we were able to generate leukemia-specific cytotoxic T lymphocytes (CTLs) capable of recognizing the leucemic cells. To identify T-cell epitopes mediating lysis of malignant cells, peptides were eluted from the patient's blasts and analyzed by mass spectrometry (LC/MS)-based peptide sequencing. Using this approach, an HLA-A24-binding peptide derived from Bax inhibitor-1 (BI-1), a regulator of apoptosis pathways, was identified as an epitope recognized by the generated CTLs. To further characterize this novel antigenic peptide, CTLs were induced using DCs electroporated with RNA coding for BI-1 or pulsed with the cognate peptide. These CTLs generated from healthy donors in vitro efficiently lysed the patient's blasts as well as other HLA-matched leukemic cells. In conclusion, we identified a BI-1 peptide as a novel immunogenic tumorassociated antigen (TAA) in AML. In vitro induction of BI-1-specific CTLs by RNA transfection or pulsing of DCs with the synthetically generated peptide was a feasible and highly effective method to generate leukemia-specific CTLs. As BI-1 is (over-) expressed in a broad variety of malignancies, it may represent an interesting novel TAA in the context of cancer vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen

et al. 2009

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“…While the function of TEGT is also unknown, its amino acid sequence predicts a 26.5 kDa integral membrane protein with seven potential transmembrane domains suggesting a possible receptor function [43]. Interestingly, TEGT is 100% homologous to BAX-inhibitor 1 (BI1) [44,45]. Studies of cells overexpressing BI1 have shown its role as a regulator of cell death pathways controlled by BCL2 and BAX [44].…”

Section: Discussionmentioning

confidence: 99%

Untitled

Smith

Shaw

et al. 2004

BMC Immunol

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BackgroundChemokines are involved in many biological activities ranging from leukocyte differentiation to neuronal morphogenesis. Despite numerous reports describing chemokine function, little is known about the molecular changes induced by cytokines.MethodsWe have isolated and identified by differential display analysis 182 differentially expressed cDNAs from CXCR3-transfected Jurkat T cells following treatment with CXCL12 or CXCL10. These chemokine-modulated genes were further verified using quantitative RT-PCR and Western blot analysis.ResultsOne hundred and forty-six of the cDNAs were successfully cloned, sequenced, and identified by BLAST. Following removal of redundant and non-informative clones, seventeen mRNAs were found to be differentially expressed post treatment with either chemokine ligand with several representing known genes with established functions. Twenty-one genes were upregulated in these transfected Jurkat cells following both CXCL12 and CXCL10, four genes displayed a discordant response and seven genes were downregulated upon treatment with either chemokine. Identified genes include geminin (GEM), thioredoxin (TXN), DEAD/H box polypeptide 1 (DDX1), growth hormone inducible transmembrane protein (GHITM), and transcription elongation regulator 1 (TCERG1). Subsequent analysis of several of these genes using semi-quantitative PCR and western blot analysis confirmed their differential expression post ligand treatment.ConclusionsTogether, these results provide insight into chemokine-induced gene activation and identify potentially novel functions for known genes in chemokine biology.

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“…BI-1 expression levels in these organs vary and fluctuate during development (Grzmil et al, 2006;Tanaka et al, 2006). During pre-and early-natal lung development BI-1 expression peaked during times of high apoptosis (Jean et al, 1999), indicating a possible link between cell-death and BI-1 expression. How BI-1 expression is regulated in tissues remains unknown, however, upstream of the bi-1 gene are two alternative promoters (P1 and P2), which are independent of TATA elements.…”

Section: Regulation Of Apoptosis By Bax Inhibitor-1mentioning

confidence: 99%

“…How BI-1 expression is regulated in tissues remains unknown, however, upstream of the bi-1 gene are two alternative promoters (P1 and P2), which are independent of TATA elements. It is thought the proximal P1 promoter is regulated by cell-type specific factors, while the distal P2 promoter is constitutive in all cell types (Jean et al, 1999). Moreover, 15 p53 tumour suppressor sites are present in the BI-1 promoter region.…”

Section: Regulation Of Apoptosis By Bax Inhibitor-1mentioning

confidence: 99%