Disease relevance of Ets1

• OBJECTIVE: To determine the relationship between hypoxia and the expression of Ets-1 and hypoxia-inducible factor 1alpha (HIF-1alpha) in both normal and inflamed joints [1].
• Expression and function of Ets-1 during experimental acute renal failure in rats [2].
• Ets-1 mRNA and protein expression were strongly increased at 6 to 24 h after the ischemia, respectively [2].
• The relative ratio of the two Ets-1 transcripts, which were shown to arise by differential polyadenylation, was not affected by provirus insertion [3].
• Mesangial cell expression of proto-oncogene Ets-1 during progression of mesangioproliferative glomerulonephritis [4].

High impact information on Ets1

• We have used a range of methods to demonstrate a strong binding between p62 and p54 in this complex and show that the rod domain of p62 appears to constitute the principal binding site for p54 [5].
• Interaction of Ets-1 and the POU-homeodomain protein GHF-1/Pit-1 reconstitutes pituitary-specific gene expression [6].
• The Ets-1-GHF-1 synergy requires a composite Ets-1-GHF-1 cis element and is dependent on an Ets-1-specific protein domain [6].
• A 4- or 10-bp insertion between muE3 and muB inactivated the mu enhancer in S194 plasma cells but did not affect in vitro binding of Ets-1, PU.1, or the muE3-binding protein TFE3, alone or in pairwise combinations [7].
• Ets-1 mRNA abundance was induced with a peak at 2 hours after stimulation with platelet-derived growth factor-BB and with angiotensin II [8].

Chemical compound and disease context of Ets1

• Inactivation of Ets 1 transcription factor by a specific decoy strategy reduces rat C6 glioma cell proliferation and mmp-9 expression [9].

Biological context of Ets1

• Shear stress induces hepatocyte PAI-1 gene expression through cooperative Sp1/Ets-1 activation of transcription [10].
• EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress [10].
• Mutation of either the Ets-1 or GHF-1 binding sites inhibits Ras and Raf activation of the rPRL promoter, and insertion of this RRE into the rat growth hormone promoter confers Ras responsiveness [11].
• Overexpression of Ets-1 in GH3 pituitary cells enhanced both basal and Ras induced activity from the 3P enhancer [12].
• Pit-1beta/GHF-2, an alternatively spliced isoform containing a 26-amino acid insert (beta-domain) within its transcription-activation domain, physically interacts with Ets-1 but fails to synergize [13].

Anatomical context of Ets1

• Overexpression of Ets-1 in cultured mesangial cells prevented transforming growth factor (TGF)-beta-induced inhibition of DNA-binding activity and TGF-beta-induced type I collagen production [14].
• In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1 [10].
• Furthermore, we find that expression of dominant negative Ets1 (N70-Ets1) inhibits both the beta-neuregulin and autocrine survival of Schwann cells [15].
• The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis [1].
• For clarifying the significance of Ets-1 in ARF, a rat ARF model in vivo and LLC-PK1 cells as an in vitro model were used [2].

Associations of Ets1 with chemical compounds

• The IL-1beta-caused increase in DNA binding of both NF-kappaB and Ets-1 immunopositive complexes was substantially suppressed by dexamethasone as shown by EMSA [16].
• 1) Purified p54 is capable of undergoing endogenous phosphorylation in the presence of [gamma-32P]ATP producing a 32P-labeled pp54 polypeptide which is specifically immunoprecipitated by TBR-sera and contains only phosphotyrosine [17].
• Transcriptional synergy was observed between the proximal VDRE and adjacent EBS as was the attendant formation of a ternary complex between vitamin D receptor- retinoid X receptor (VDR. RXR) and Ets-1 [18].
• Hydrogen peroxide (H2O2) at nanomolar concentrations stimulated levels of Ets-1 and increased PDGF-Ralpha transcription and mRNA expression without affecting Sp1 expression [19].
• The current study demonstrates that overexpression of the dominant negative form of JNK1 or p54 JNK2/SAPKbeta reduces Cox-2 expression and PGE2 production stimulated by IL-1beta [20].

Physical interactions of Ets1

• Electrophoretic mobility shift assays revealed that Ets-1 interacts selectively with the -1350GGAA-1347 Ets element in the p21WAF1/Cip1 promoter [21].
• A gel shift assay demonstrated that Ets-1 binds to the ets-1 binding site of the cyclin D1 promoter in the ischemia-reperfusion condition [2].

Regulatory relationships of Ets1

• Using transient transfection and Western blot analysis, we determined that Ets-1 activates p21WAF1/Cip1 transcription and protein expression [21].
• The Ets-1 pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF [2].
• These findings suggested that ICAM-1 in endothelial cells may act as a signaling receptor to induce Ets-1 expression, whereas E-selectin seems to function in the formation of tubelike structures in vascular endothelial cell cultures [22].
• Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cycloheximide [23].
• Ets-1 is a transcription factor known to control the expression of genes involved in extracellular matrix remodeling [24].

Other interactions of Ets1

• In addition, exogenous Ets-1 abolished TGF-beta-induced collagen gel contraction [14].
• CONCLUSIONS: The Ets-1 transcriptional factor may participate in IL-1beta-mediated MMP-9 expression in tubulointerstitial cells [25].
• In contrast, the -1577GGAT-1574 motif mediates basal but not Ets-1 activation of the p21WAF1/Cip1 promoter [21].
• We confirm that Ets-1 or a related Ets factor is the nuclear target of the Ras pathway leading to activation of the rPRL promoter and demonstrate that Elk-1 and Net do not mediate the Ras response [11].
• Using a series of site-specific mutations and deletions of the proximal rPRL promoter we have mapped the major Ras/Raf response element (RRE) to a composite Ets-1/GHF-1 binding site located between positions -217 and -190 [11].

Analytical, diagnostic and therapeutic context of Ets1

• Hypoxyprobe-1 adducts, Ets-1, and HIF-1alpha were localized in the joints of the hind feet from these groups using immunohistochemistry [1].
• Co-immunoprecipitation and co-transfection analysis showed that Ets-1 binds p300 and cooperatively activates p21WAF1/Cip1 transcription [21].
• Overexpression of Ets-1 did not significantly change the caspase 3 activity or the value of cell death ELISA in LLC-PK1 cells [2].
• Sequence analysis of a near-full-length (4,991-bp) cDNA clone of the 5.5-kb RNA revealed a 441-amino-acid open reading frame encoding a protein identical to the human and mouse Ets-1 proteins with the exception of five and nine species-specific conservative amino acid differences, respectively [3].
• Changes in Ets-1 mRNA levels were detected by in situ hybridization and Northern blotting [4].

References