The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3

Weidenfeld-Baranboim, Keren; Hasin, Tal; Darlyuk, Ilona; Heinrich, Ronit; Elhanani, Ofer; Pan, Jianzhi; Yokoyama, Kazunari K.; Aronheim, Ami

doi:10.1093/nar/gkp083

Cited by 40 publications

(36 citation statements)

References 33 publications

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“…A gene ontology classification allowed us to focus on proteins known to be regulators of transcription. Previous studies have shown that ATF3 forms homodimer and heterodimer complexes with basic leucine zipper proteins to regulate target genes both positively and negatively (31,47,48). Our results showed that ATF3 associated with ATF2, JDP2, HDAC6, and HDAC7 (Tables 2 and 3).…”

Section: Discussionsupporting

confidence: 63%

Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression

Zhou

Loberg

et al. 2016

Molecular and Cellular Biology

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P lacenta growth factor (PlGF), an angiogenic growth factor of the vascular endothelial growth factor (VEGF) family, has pleiotropic and redundant roles in development but features prominently in various pathological conditions such as ischemia, angiogenesis, inflammation, atherosclerosis, preeclampsia, and diabetic wound healing (1-9). PlGF expression is induced by hypoxia, erythropoietin, and iron; PlGF effects are manifested via binding to its sole cognate receptor, VEGF receptor 1 (VEGFR-1) (10-13).Recent studies have shown that plasma levels of PlGF are abnormally high in patients with hemolytic anemias, such as in sickle cell disease (SCD) (12,14). Moreover, high plasma PlGF levels correlate with increased incidence of vaso-occlusive events in SCD subjects (12). Consistent with these findings, plasma levels of plasminogen activator inhibitor 1 (PAI-1) and endothelin-1 (ET-1) are high in a mouse model of sickle cell disease, namely, Berkeley sickle (BK-SS) mice, which also show high plasma PlGF levels (15, 16). Conversely, PlGF knockout mice exhibit low plasma PlGF levels and low plasma levels of PAI-1 and ET-1 (15, 16). Furthermore, augmentation of erythroid PlGF expression in normal mice to the levels seen in sickle mice results in increased production of endothelin-1 with associated pulmonary changes, as seen in pulmonary hypertension (PH) in SCD (16); these results were corroborated in a study of 123 patients with SCD (16). Thus, studies in vitro and in vivo support the crucial role of PlGF in upregulating the expression of ET-1 in endothelial cells and associated pulmonary changes characteristic of pulmonary hypertension in SCD.We show that PlGF activates endothelial cells to upregulate the expression of genes such as the ET-1 and PAI-1 genes via activation of hypoxia-inducible factor 1 (HIF-1␣), independently of hypoxia (15,17). Moreover, we have shown that posttranscriptional regulation of ET-1 and PAI-1 is achieved by microRNA 199a2 (miR-199a2), which targets the 3= untranslated region (UTR) of HIF-1␣ mRNA (18).The DNM3 opposite strand (DNM3os) gene produces a noncoding RNA (ncRNA) that serves as the precursor of miR-199a2 and miR-214 (18). This locus is located within an intron of DNM3 and is transcribed from the opposite strand, hence, its designation. Transcription of DNM3os and of cotranscribed miR-199a2/miR-214 is greatly attenuated by PlGF, thus allowing unhindered expansion of HIF-1␣ activity and expression of genes, i.e., the ET-1 and PAI-1 genes, requiring this transcription factor, (18). However, the molecular mechanism of PlGF-mediated downregulation of miR-199a2/miR-214 and DNM3os ncRNA is not fully understood.In the present study, we show that repression of DNM3os in response to PlGF required the participation of activated transcription factor 3 (ATF3), which binds to ATF3 response elements in the DNM3os promoter. The ATF3 gene, a stress-inducible gene, has been shown to play important roles in several pathological conditions, including host immunity and cancer (19-21). To de- Citation...

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Section: Discussionsupporting

confidence: 63%

Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression

Zhou

Loberg

et al. 2016

Molecular and Cellular Biology

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“…Evidence for a regulatory role for ATF3 in neutrophil development has been described. 37 JDP2 is an important negative regulator of ATF3 expression [37][38][39] whose depletion results in elevated Atf3 expression, decreased Ly6G expression (a neutrophil maturation marker), and defective effector function (eg, superoxide production, neutrophil extracellular trap formation). 37 Ectopic ATF3 overexpression throughout neutrophil differentiation recapitulated the immature phenotype of JDP2 2/2 neutrophils.…”

Section: Discussionmentioning

confidence: 99%

ATF3 is a novel regulator of mouse neutrophil migration

Boespflug

Kumar

McAlees

et al. 2014

Blood

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“…Some of the JUN/FOS proteins are induced during the AAR (30), and the increase in cJUN expression occurs by a process that is independent of ATF4 signaling (10). ATF/CRE elements have been identified within the ATF3 gene (16,37), and in particular, an ATF/CRE site (nt Ϫ93/Ϫ85) exists upstream of the ATF3 CARE site (nt Ϫ23/Ϫ15). One member of the JUN family, JunB, has been reported to act via this site to regulate ATF3 expression (13).…”

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confidence: 99%

Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

Kilberg

2013

Physiological Genomics

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The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3

Cited by 40 publications

References 33 publications

Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression

Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression

ATF3 is a novel regulator of mouse neutrophil migration

Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

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