Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells

Bates, Elizabeth E. M.; Ravel, Odile; Dieu, M.C.; Ho, Stephen; Guret, Christiane; Bridon, Jean-Michel; Aït-Yahia, Smina; Brière, Francine; Caux, Christophe; Banchereau, Jacques; Lebecque, Serge

doi:10.1002/eji.1830271002

Cited by 92 publications

(84 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43 Elevated FAT10 expression in mature B cells and dendritic cells has also suggested a potential role of FAT10 in antigen presentation. 44 IRF4 is a lymphoid-specific member of the IRF family of transcription factors. It was also shown to be upregulated in antrum infected with H. pylori.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

View full text Add to dashboard Cite

Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

show abstract

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

View full text Add to dashboard Cite

show abstract

“…FAT10 gene is localized to the telomeric end of the cluster of human major histocompatibility complex (MHC) class I (Fan et al, 1996) genes. In addition, it is expressed in dendritic cells and mature B cells (Bates et al, 1997) and can be synergistically induced by the IFNg and TNF-a cytokines (Raasi et al, 1999). Although the FAT10 gene resides at the telomeric end of the MHC class I genes, it was reported not to be a member of this class of genes Kumanovics et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers

2006

View full text Add to dashboard Cite

FAT10 is a member of the ubiquitin-like modifier family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 5 0 untranslated region (5 0 UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5 0 UTR (from þ 26 to À1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant downregulation (Po0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 5 0 half consensus sequence of p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis.

show abstract

“…UBD has been initially cloned as a gene exclusively expressed in dendritic cells and mature B cells. 46 It was reported to be involved in protein degradation, apoptosis, and control of spindle assembly. 47,48 Moreover, UBD expression can be induced by IFNg, whereas another IFNg inducible gene, NEDD8 ultimate buster-1L (NUB1L), has been reported to accelerate the degradation of UBD.…”

Section: Discussionmentioning

confidence: 99%

UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells

Ocklenburg

Moharregh-Khiabani

Geffers

et al. 2006

Laboratory Investigation

View full text Add to dashboard Cite

Here, we report the identification of the ubiquitin-like gene UBD as a downstream element of FOXP3 in human activated regulatory CD4 þ CD25 hi T cells (T reg ). Retroviral transduction of UBD in human allo-reactive effector CD4 þ T helper (T h ) cells upregulates CD25 and mediates downregulation of IL4 and IL5 expression similar to overexpression of FOXP3. Moreover, UBD impairs T h cell proliferation without upregulation of FOXP3 and impairs calcium mobilization. In the presence of ionomycin, overexpression of UBD in T h cells leads to the induction of IL1R2 that resemble FOXP3-transduced T h cells and naturally derived T reg cells. A comparison of the transcriptome of FOXP3-and UBD-transduced T h cells with T reg cells allowed the identification of the gene LGALS3. However, high levels of LGALS3 protein expression were observed only in human CD4 þ CD25 hi derived T reg cells and FOXP3-transduced T h cells, whereas little was induced in UBD-transduced T h cells. Thus, UBD contributes to the anergic phenotype of human regulatory T cells and acts downstream in FOXP3 induced regulatory signaling pathways, including regulation of LGALS3 expression. High levels of LGALS3 expression represent a FOXP3-signature of human antigen-stimulated CD4 þ CD25 hi derived regulatory T cells.

show abstract

Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells

Cited by 92 publications

References 32 publications

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers

UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells

Contact Info

Product

Resources

About