A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α<sub>2</sub>(I) and Other Promoters

Zhu, Xiaojuan; Ting, Jenny P.‐Y.

doi:10.1128/mcb.21.20.7078-7088.2001

Cited by 64 publications

(110 citation statements)

References 65 publications

(72 reference statements)

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“…Ectopic CIITA expression in Tg mice, or its absence in knockout mice, has no significant repercussions on expression of the Tap1, Yars, Eif3s2, Kpna6, Ctse, Col1a2, Ptprr, Tnfsf6 and Plxna1 genes, despite previous evidence suggesting they might be regulated by CIITA [9,10,[12][13][14]20]. Several explanations could account for this discrepancy.…”

Section: Discussionmentioning

confidence: 83%

“…This suggests that CIITA is highly dedicated to the regulation of MHC-II expression. Nevertheless, a series of reports have implicated CIITA in the regulation of a wide variety of other genes functioning within and outside the immune system [8][9][10][11][12][13][14]20]. These reports suggested that CIITA might play a pleiotropic role in various biological processes.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to MHC-II expression, there is little or no evidence for a positive or negative correlation, respectively, between the abundance of CIITA mRNA and expression of the genes that have been suggested to be activated or repressed by CIITA (supplementary Fig. 2) [10,12,13].…”

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

“…Those encoding cathepsin E and IL-10 were suggested to be repressed by CIITA in mouse B cells and/or DC [10,11]. The genes encoding collagen type Ia2, thymidine kinase and cyclin D1 were proposed to be repressed by CIITA in IFN-c-induced cells [12]. A microarray analysis identified 16 additional genes of diverse functions that were proposed to be downregulated by CIITA in a human B cell line [13].…”

Section: Molecular Immunologymentioning

confidence: 99%

“…Among the genes proposed to be activated by CIITA, we chose those encoding TGFb RIP1 (Eif3s2), Importin a7 (Kpna6), Tap1 (Tap1), and tyrosyl-tRNA synthetase (Yars) [13]. Among the genes suggested to be repressed by CIITA, we selected those encoding collagen type I a2 (Col1a2), cathepsin E (Ctse), tyrosine phosphatase receptor (Ptprr) and FasL (Tnfsf6) [9,10,12,13].…”

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

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Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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CIITA is a master regulatory factor for the expression of MHC class II (MHC-II) and accessory genes involved in Ag presentation. It has recently been suggested that CIITA also regulates numerous other genes having diverse functions within and outside the immune system. To determine whether these genes are indeed relevant targets of CIITA in vivo, we studied their expression in CIITA-transgenic and CIITA-deficient mice. In contrast to the decisive control of MHC-II and related genes by CIITA, nine putative non-MHC target genes (Eif3s2, Kpna6, Tap1, Yars, Col1a2, Ctse, Ptprr, Tnfsf6 and Plxna1) were found to be CIITA independent in all cell types examined. Two other target genes, encoding IL-4 and IFN-c, were indeed found to be up-and down-regulated, respectively, in CIITA-transgenic CD4 + T cells. However, there was no correlation between MHC-II expression and this Th2 bias at the level of individual transgenic T cells, indicating an indirect control by CIITA. These results show that MHC-II-restricted Ag presentation, and its indirect influences on T cells, remains the only pathway under direct control by CIITA in vivo. They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

Section: Molecular Immunologymentioning

confidence: 99%

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

See 3 more Smart Citations

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

et al. 2004

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The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigations, the major target genes of CIITA remain those implicated in the presentation of antigenic peptides by MHCII molecules. Although other putative target genes have been reported, the contribution of CIITA to their expression remains indirect, controversial or comparatively minor relative to its decisive role as a regulator of MHCII and related genes. Second, the most important parameter dictating MHCII expression is by far the expression pattern of the gene encoding CIITA (MHC2TA). The vast majority of signals that activate or repress MHCII expression under physiological and pathological situations converge on one or more of the three alternative promoters that drive transcription of the MHC2TA gene. In short, with respect to its specificity and its exquisitely controlled pattern of expression, CIITA is by a long stretch the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen-presentation.

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Inhibition of collagen gene expression by interferon‐γ: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ)

Ghosh

Bhattacharyya

Mori

et al. 2005

Journal Cellular Physiology

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By inhibiting collagen synthesis, interferon-gamma (IFN-gamma) plays a key role in maintaining connective tissue homeostasis, but the mechanisms are not well-understood. In addition to intracellular signaling through the canonical JAK-STAT transduction pathway, IFN-gamma was recently shown to regulate gene expression via the CCAAT/enhancer-binding protein beta (C/EBPbeta) as well. Because C/EBPbeta is a crucial mediator of immune and inflammatory responses, and has been implicated in regulation of collagen synthesis by tumor necrosis factor-alpha, we examined its role in the inhibitory effects of IFN-gamma. The results demonstrated that IFN-gamma caused increased C/EBPbeta expression in dermal fibroblasts and enhanced its binding to cognate DNA sequences in the alpha2(I) procollagen gene (COL1A2) promoter in vitro and in vivo. Disruption of C/EBP binding by deletion or site-directed mutagenesis abrogated the inhibition of collagen promoter activity in transient transfection assays, as did cotransfection with dominant negative C/EBPbeta, indicating a functional role of cellular C/EBPbeta in mediating the IFN-gamma response. Rapid phosphorylation of the ERK1/2 MAP kinases induced by IFN-gamma was accompanied by phosphorylation and nuclear translocation of cellular C/EBPbeta, and pretreatment of fibroblasts with ERK1/2 kinase inhibitor blocked C/EBPbeta phosphorylation, as well as inhibition of COL1A2 promoter activity, elicited by IFN-gamma. These results provide compelling evidence for a novel C/EBPbeta-dependent IFN-gamma signaling pathway responsible for inhibition of collagen gene transcription. Taken together with recent reports, the findings indicate that intracellular pathways mediating negative regulation of collagen synthesis in response to distinct inflammatory signals that converge on C/EBPbeta.

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A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α₂(I) and Other Promoters

Cited by 64 publications

References 65 publications

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

Inhibition of collagen gene expression by interferon‐γ: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ)

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A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α2(I) and Other Promoters

Cited by 64 publications

References 65 publications

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

Inhibition of collagen gene expression by interferon‐γ: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ)

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A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α₂(I) and Other Promoters