c-Jun Homodimers Can Function as a Context-Specific Coactivator

Grondin, Benoı̂t; Lefrançois, Martin; Tremblay, Mathieu; Saint-Denis, Marianne; Haman, André; Waga, Kazuo; Bédard, André; Tenen, Daniel G.; Hoang, Trang

doi:10.1128/mcb.00936-06

Cited by 45 publications

(47 citation statements)

References 84 publications

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“…Interestingly, the M-CSF receptor promoter has no consensus binding site for c-Jun transcription factor (37). As a consequence, c-Jun does not directly bind to M-CSF receptor promoter, but it associates with PU.1 and C/EBP␤ via its basic domain (34,37). Moreover, co-activator c-Jun recruitment by C/EBP␤ to DNA facilitates RNA polymerase II recruitment (34).…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence, c-Jun does not directly bind to M-CSF receptor promoter, but it associates with PU.1 and C/EBP␤ via its basic domain (34,37). Moreover, co-activator c-Jun recruitment by C/EBP␤ to DNA facilitates RNA polymerase II recruitment (34). c-Jun, PU.1, and C/EBP␤ have been shown to physically interact with each other and enhance the transcription of monocyte-specific genes via binding to their respective sites on DNA (33,54).…”

Section: Discussionmentioning

confidence: 99%

“…c-Jun does not directly bind to the M-CSF receptor promoter but enhances the ability of PU.1 to transactivate it (37). Synergism among PU.1, C/EBPs, and c-Jun is essential to activate monocyte target genes (34). Among these, M-CSF receptor is critical for monocyte cell survival and proliferation and is activated early during the monocyte differentiation process (38 -40).…”

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confidence: 99%

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Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

Ceccarelli

Racanicchi

Martelli

et al. 2011

Journal of Biological Chemistry

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Polyunsaturated fatty acids (PUFAs) inhibit proliferation and induce differentiation in leukemia cells. To investigate the molecular mechanisms whereby fatty acids affect these processes, U937 leukemia cells were conditioned with stearic, oleic, linolenic, ␣-linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids. PUFAs affected proliferation; eicosapentaenoic acid (EPA) was the most potent on cell cycle progression. EPA enhanced the expression of the myeloid lineage-specific transcription factors CCAAT/enhancer-binding proteins (C/EBP␤ and C/EBP␦), PU.1, and c-Jun, resulting in increased expression of the monocyte lineage-specific target gene, the macrophage colony-stimulating factor receptor. Indeed, it is known that PU.1 and C/EBPs interact with their consensus sequences on a small DNA fragment of macrophage colony-stimulating factor receptor promoter, which is a determinant for expression. We demonstrated that C/EBP␤ and C/EBP␦ bind the same response element as a heterodimer. We focused on the enhanced expression of C/EBP␦, which has been reported to be a tumor suppressor gene silenced by promoter hypermethylation in U937 cells. After U937 conditioning with EPA and bisulfite sequencing of the ؊370/؊20 CpG island on the C/EBP␦ promoter region, we found a site-specific CpG demethylation that was a determinant for the binding activity of Sp1, an essential factor for C/EBP␦ gene basal expression. Our results provide evidence for a new role of PUFAs in the regulation of gene expression. Moreover, we demonstrated for the first time that re-expression of the tumor suppressor C/EBP␦ is controlled by the methylation state of a site-specific CpG dinucleotide.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

Ceccarelli

Racanicchi

Martelli

et al. 2011

Journal of Biological Chemistry

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“…The above results led us to address the question whether C/EBPα actually recruits RARα-PLZF to target promoters. To this end, we designed a DNA capture assay (29) in which the −74 to +67 region of the Csf3r promoter was immobilized on magnetic beads and incubated with nuclear extracts from C/EBPα− and control TAP-or RP-TAP-expressing cells (Fig. 3E).…”

Section: Rarα-plzf Decreases the Expression Of C/ebpα Target Genes Wimentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) assays were performed as described previously (29,38) using 500 μg of protein per sample and anti-acetyl histone H3 (Upstate Biotechnologies) or normal rabbit serum as control. Primer sequences are shown in SI Materials and Methods and Table S1.…”

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confidence: 99%

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

Girard

Tremblay

Humbert

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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In acute promyelocytic leukemia, granulocytic differentiation is arrested at the promyelocyte stage. The variant t(11;17) translocation produces two fusion proteins, promyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) and RARα-PLZF, both of which participate in leukemia development. Here we provide evidence that the activity of CCAAT/enhancer binding protein α (C/EBPα), a master regulator of granulocytic differentiation, is severely impaired in leukemic promyelocytes with the t(11;17) translocation compared with those associated with the t(15;17) translocation. We show that RARα-PLZF inhibits myeloid cell differentiation through interactions with C/EBPα tethered to DNA, using ChIP and DNA capture assays. Furthermore, RARα-PLZF recruits HDAC1 and causes histone H3 deacetylation at C/EBPα target loci, thereby decreasing the expression of C/EBPα target genes. In line with these results, HDAC inhibitors restore in part C/EBPα target gene expression. These findings provide molecular evidence for a mechanism through which RARα-PLZF acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with C/EBPα and inhibiting its activity.APL | granulocyte differentiation | transcription inhibition | histone modification | protein interaction

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JunB can enhance the transcription of IL‐8 in oral squamous cell carcinoma

Tsunoda

Fukasawa

Nishihara

et al. 2020

Journal Cellular Physiology

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Proteasome inhibitor MG132 was shown to enhance the secretion of interleukin 8 (IL-8) by various cells. The enhancement is regulated by the transcription factor activator protein-1 (AP-1) at the transcriptional level. AP-1 is a dimer formed by AP-1 family proteins. The purpose of the present study was to explore the combinations of the AP-1 family proteins that contribute to MG132-driven IL-8 secretion. Oral squamous cell carcinoma-derived cell lines, Ca9-22 and HSC3, were used to demonstrate their response to MG132. IL-8 secretion was augmented by MG132 in both cell lines. c-Jun expression was detected in both the cell lines, whereas c-Fos expression was detected only in the HSC3. The influence of MG132 stimulation on c-Jun and c-Fos expression was further examined by western blot analysis. c-Jun expression was increased by MG132 stimulation, whereas c-Fos expression was not detected even after MG132 stimulation. As JunB is reported to inhibit the transcriptional activity of the AP-1 complex, we speculated that the c-Jun homodimer should contribute to IL-8 enhancement. Expression vectors encoding wild type and c-Jun mutants, M17 and M22-23, respectively, were constructed and transfected into the Ca9-22 cells. In contrast to our expectations, MG132-induced IL-8 secretion was significantly reduced in all the transfectants suggesting that other c-Jun members might form homodimers with c-Jun and contribute to IL-8 enhancement. Transfection of the cells with c-Jun or JunB small hairpin RNA (shRNA) reduced IL-8 secretion up to 50% and 65% of the control shRNA transfectant. Furthermore, cotransfection of both shRNA almost completely inhibited the IL-8 secretion. These results indicate that JunB not only inhibits but also enhances the transcription of c-Jun targets in combination with c-Jun.

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c-Jun Homodimers Can Function as a Context-Specific Coactivator

Cited by 45 publications

References 84 publications

Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

JunB can enhance the transcription of IL‐8 in oral squamous cell carcinoma

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