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Early Growth Response (early + growth_response)
Selected AbstractsEarly growth response 2 regulates the survival of thymocytes during positive selectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Victoria J. Lawson Abstract The early growth response (Egr) transcription factor family regulates multiple steps during T-cell development. We examine here the role played by Egr2 in positive selection. In double-positive cells, Egr2 is upregulated immediately following TCR ligation, and its expression requires both the MAPK and calcineurin signaling pathways. Inducible transgenic and knockout mice were generated to cause gain- or loss-of-function of Egr2 in double-positive cells, and had reciprocal effects; more mature single-positive cells were made when Egr2 was overexpressed, and fewer when Egr2 was absent. These defects were associated with changes in the survival of positively selected cells rather than perturbation of positive selection or immediate post-selection signaling. The survival function of Egr2 at least partly depends upon its ability to activate the cytokine-mediated survival pathway, likely through negative regulation of both the IL-7R and suppressor of cytokine signaling 1 (Socs1), the molecular switch whose downregulation normally results in restored responsiveness to cytokine signaling following selection. While gain of Egr2 caused a decrease in Socs1 mRNA, loss of Egr2 resulted in downregulation of IL-7R, upregulation of Socs1, and inhibition of Stat5 phosphorylation and IL-7-mediated survival post-selection. Therefore, expression of Egr2 following positive selection links the initial TCR signaling event to subsequent survival of signaled cells. [source] Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations,HUMAN MUTATION, Issue 5 2002Chikahiko Numakura Abstract Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder and is traditionally classified into two major types, CMT type 1 (CMT1) and CMT type 2 (CMT2). Most CMT1 patients are associated with the duplication of 17p11.2-p12 (CMT1A duplication) and small numbers of patients have mutations of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), connexin 32 (Cx32/GJB1), and early growth response 2 (EGR2) genes. Some mutations of MPZ and Cx32 were also associated with the clinical CMT2 phenotype. We constructed denaturing gradient gel electrophoresis (DGGE) analysis as a screening method for PMP22, MPZ, and Cx32 mutations and studied 161 CMT patients without CMT1A duplication. We detected 27 mutations of three genes including 15 novel mutations; six of PMP22, three of MPZ, and six of Cx32. We finally identified 21 causative mutations in 22 unrelated patients and five polymorphic mutations. Eighteen of 22 patients carrying PMP22, MPZ, or Cx32 mutations presented with CMT1 and four of them with MPZ or Cx32 mutations presented with the CMT2 phenotype. DGGE analysis was sensitive for screening for those gene mutations, but causative gene mutation was not identified in many of the Japanese patients with CMT, especially with CMT1. Other candidate genes should be studied to elucidate the genetic basis of Japanese CMT patients. Hum Mutat 20:392,398, 2002. © 2002 Wiley-Liss, Inc. [source] Prostanoids induce egr1 gene expression in cementoblastic OCCM cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2007L. Pham Background and Objective:, Prostanoids that activate protein kinase C signaling are potent anabolic stimulators of cementoblastic OCCM cells. Using cDNA subtractive hybridization, we identified early growth response gene-1 (egr1) as a prostanoid-induced gene. Egr1, a zinc-finger transcription factor expressed during tooth development, regulates cell growth and differentiation. We hypothesize that Egr1 may mediate part of the prostanoid-induced anabolic effect in cementoblasts. Our objective was to characterize prostanoid-induced egr1 gene expression in OCCM cells. Material and Methods:, Total RNA and proteins were assayed by northern blot and western immunoblot assays. Results:, Prostaglandin E2 -, prostaglandin F2, - and fluprostenol-induced egr1 mRNA levels peaked at 0.5 h and returned to baseline by 4 h. Prostaglandin F2, and fluprostenol more potently induced egr1 compared with prostaglandin E2. The phorbol ester, phorbol 12-myristate 13-acetate, which activates protein kinase C signaling, induced egr1 mRNA levels 66-fold over the control, whereas forskolin (a cAMP-protein kinase A activator) and ionomycin (a calcium activator) had no effect. Protein kinase C inhibition significantly inhibited prostaglandin E2 -, prostaglandin F2, - and fluprostenol-induced egr1 mRNA levels. Finally, prostanoids maximally induced Egr1 protein at 1 h. Conclusion:,egr1 is a primary response gene induced by prostaglandin E2, prostaglandin F2, and fluprostenol in OCCM cells through protein kinase C signaling, suggesting that Egr1 may be a key mediator of anabolic responses in cementoblasts. Cementum is vital for periodontal organ maintenance and regeneration. Periodontal ligament fibers (Sharpey's fibers) insert into bone and cementum, thereby supporting the tooth in the alveolus (1). If the periodontal organ is lost, its regeneration requires cementoblast differentiation in order to form new cementum for periodontal ligament fiber insertion. Early attempts to regenerate cementum have proven difficult and rarely generate sufficient tissue (2). A better understanding of the molecular and cellular regulators that promote cementoblast differentiation is critical for developing targeted periodontal regeneration. [source] 1,1-bis(3,-indolyl)-1-(p -methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cellsMOLECULAR CARCINOGENESIS, Issue 4 2008Sung Dae Cho Abstract 1,1-Bis(3,-indolyl)-1-(p -methoxyphenyl)methane (DIM-C-pPhOCH3) is a methylene-substituted diindolylmethane (C-DIM) analog that activates the orphan receptor nerve growth factor-induced-B, (NGFI-B,, Nur77). RNA interference studies with small inhibitory RNA for Nur77 demonstrate that DIM-C-pPhOCH3 induces Nur77-dependent and -independent apoptosis, and this study has focused on delineating the Nur77-independent proapoptotic pathways induced by the C-DIM analog. DIM-C-pPhOCH3 induced caspase-dependent apoptosis in RKO colon cancer cells through decreased mitochondrial membrane potential which is accompanied by increased mitochondrial bax/bcl-2 ratios and release of cytochrome c into the cytosol. DIM-C-pPhOCH3 also induced phosphatidylinositol-3-kinase-dependent activation of early growth response gene-1 which, in turn, induced expression of the proapoptotic nonsteroidal anti-inflammatory drug-activated gene-1 (NAG1) in RKO and SW480 colon cancer cells. Moreover, DIM-C-pPhOCH3 also induced NAG-1 expression in colon tumors in athymic nude mice bearing RKO cells as xenografts. DIM-C-pPhOCH3 also activated the extrinsic apoptosis pathway through increased phosphorylation of c- jun N-terminal kinase which, in turn, activated C/EBP homologous transcription factor (CHOP) and death receptor 5 (DR5). Thus, the effectiveness of DIM-C-pPhOCH3 as a tumor growth inhibitor is through activation of Nur77-dependent and -independent pathways. © 2007 Wiley-Liss, Inc. [source] | ||||||||||