Transcriptional regulation in the immune system: all roads lead to AP-1

Foletta, Victoria C.; Segal, David; Cohen, Donna R.

doi:10.1002/jlb.63.2.139

Cited by 351 publications

(274 citation statements)

References 204 publications

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“…Interestingly, Ets and AP-1 binding sites occur in a large number of promoter/enhancer elements, and functional cooperation between Ets and AP-1 is critical for controlled expression of many genes, including cytokines (47,51,52). It is notable, though, that AP-1 is not only activated in T cells following TCR cross-linking, but can be a consequence of a broad spectrum of stimuli in a variety of cells (53). Thus, it is still possible that under the appropriate circumstances activation of this pathway could lead to the expression of Jak3 in nonlymphoid cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Analysis of the Proximal Janus Kinase 3 Promoter

Aringer

Hofmann

Frucht

et al. 2003

The Journal of Immunology

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Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling via cytokine receptors that comprise the common γ-chain (γc), i.e., the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is preferentially expressed in hemopoietic cells and is up-regulated upon cell differentiation and activation. Despite the importance of Jak3 in lymphoid development and immune function, the mechanisms that govern its expression have not been defined. To gain insight into this issue, we set out to characterize the Jak3 promoter. The 5′-untranslated region of the Jak3 gene is interrupted by a 3515-bp intron. Upstream of this intron and the transcription initiation site, we identified an ∼1-kb segment that exhibited lymphoid-specific promoter activity and was responsive to TCR signals. Truncation of this fragment revealed that core promoter activity resided in a 267-bp fragment that contains putative Sp-1, AP-1, Ets, Stat, and other binding sites. Mutation of the AP-1 sites significantly diminished, whereas mutation of the Ets sites abolished, the inducibility of the promoter construct. Chromatin immunoprecipitation assays showed that histone acetylation correlates with mRNA expression and that Ets-1/2 binds this region. Thus, transcription factors that bind these sites, especially Ets family members, are likely to be important regulators of Jak3 expression.

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Section: Discussionmentioning

confidence: 99%

Characterization and Analysis of the Proximal Janus Kinase 3 Promoter

Aringer

Hofmann

Frucht

et al. 2003

The Journal of Immunology

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“…2 Triggering of this conserved TLR signal transduction converges in the activation of the transcription factors nuclear factor (NF)-kB and AP-1, which control the expression of key immunoregulatory genes. 3,4 At first, binding of ligands to TLRs recruits a central adaptor, MyD88, shared by almost all TLRs, with the exception of TLR3. Hereupon, MyD88 associates with members of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) family.…”

Section: Introductionmentioning

confidence: 99%

Post-transcriptional regulation of adapter molecules by IL-10 inhibits TLR-mediated activation of antigen-presenting cells

et al. 2008

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“…20 Homodimers of c-Jun or heterodimers of c-Jun and c-Fos modulate several biological responses by binding to the DNA consensus sequence TGA(C/G)TCA (12-o-tetradecanoylphorbol 13-acetate-responsive element of TRE) found in the promoter region of several genes. 21 There is ample evidence that the activity of AP-1, especially that of c-Jun, is essential for cell proliferation and differentiation. Recently, it has been suggested that certain components of AP-1 may also be involved in programmed cell death (PCD).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it has been suggested that certain components of AP-1 may also be involved in programmed cell death (PCD). 20,21 However, the available information is contro-versial, showing a scenario where AP-1 activity is essential for cells to undergo apoptosis under certain conditions such as cytokine withdrawal, 22 but may not be linked to cell death in the case of TNF-a or Fas-induced apoptosis. 23,24 In the present study we investigated whether binding of Gal-1 to mature T cells triggers activation of AP-1 and modulates expression of the c-Jun proto-oncogene.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2

et al. 2000

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Galectins are emerging as a new class of bioactive molecules with specific immunomodulatory properties. Galectin-1 (Gal-1), a member of this family, has been shown to induce apoptosis of mature T cells and immature thymocytes. To gain insight into the intracellular signals transduced by Gal-1 upon binding to mature T cells, we investigated whether this protein triggered activation of the dimeric AP-1 transcription factor. A marked increase in the binding of nuclear extracts to synthetic oligonucleotides containing the AP-1 consensus sequence, could be detected by an electrophoretic mobility shift assay, when T cells were cultured for 30 min in the presence of Gal-1. This DNA-binding activity was preceded by a rapid increase in the levels of c-Jun mRNA, as determined by Northern blot analysis. Requirement of AP-1 for Gal-1-induced apoptosis was confirmed by the dosedependent reduction on the level of DNA fragmentation observed when cells were pre-treated with curcumin (an inhibitor of AP-1 activation) before exposure to Gal-1. Finally, evidence is also provided by Western blot analysis, showing that Gal-1 inhibits Concanavalin A (Con A) induction of Bcl-2 protein. Results presented in this study provide the first experimental evidence regarding AP-1 and Bcl-2 as targets of the signal transduction pathway triggered by Gal-1 and set the basis for a more in depth understanding of the molecular mechanisms of T-cell death regulation. Cell Death and Differentiation (2000) 7, 747 ± 753.

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Transcriptional regulation in the immune system: all roads lead to AP-1

Cited by 351 publications

References 204 publications

Characterization and Analysis of the Proximal Janus Kinase 3 Promoter

Characterization and Analysis of the Proximal Janus Kinase 3 Promoter

Post-transcriptional regulation of adapter molecules by IL-10 inhibits TLR-mediated activation of antigen-presenting cells

Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2

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