Disease relevance of Ier2

• Restriction-mediated differential display (RMDD) identifies pip92 as a pro-apoptotic gene product induced during focal cerebral ischemia [1].
• RESULTS: mRNA for Cyr61, a secreted growth factor-inducible immediate early gene, was markedly up-regulated at two hours in the kidney but not other organs following renal ischemia [2].
• Insulin induction of pip 92, CL-6, and novel mRNAs in rat hepatoma cells [3].

High impact information on Ier2

• The growth factor-inducible immediate-early gene 3CH134 encodes a protein-tyrosine-phosphatase [4].
• The chx1 gene is remarkable in its lack of detectable introns and of strong bias against CpG dinucleotides [5].
• Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion [6].
• cyr61 was first identified as a growth factor-inducible immediate-early gene in mouse fibroblasts [6].
• pip92 is a cellular immediate-early gene inducible by serum growth factors in fibroblasts [7].

Biological context of Ier2

• Here we show that a 73-base pair pip92 promoter fragment located between base pairs 1231 and 1158 upstream of the transcription start site is sufficient to mediate transcriptional activation [8].
• Here we demonstrate that pip92 induces cell death in primary neurons and displays several hallmarks of pro-apoptotic activity upon overexpression, supporting the notion that we have identified a novel pathophysiological player in cerebral ischemia [1].
• One particularly interesting gene, whose upregulation by ischemia has not been described before, is pip92; this gene shows a rapid and long-lasting induction after cerebral ischemia [1].
• We describe herein a previously unrecognized regulator of mammalian chondrogenesis encoded by a murine growth factor-inducible immediate-early gene, cyr61 [9].
• Deletion analysis of the pip92 promoter indicated that pip92 activation occurs primarily within the region containing a serum response element (SRE) [10].

Anatomical context of Ier2

• Pip92: a short-lived, growth factor-inducible protein in BALB/c 3T3 and PC12 cells [7].
• Cyr61, product of a growth factor-inducible immediate-early gene, regulates chondrogenesis in mouse limb bud mesenchymal cells [9].
• A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus [11].
• The region-specific activation of pip92 in the CNS was observed 3 h after NMDA injection, and high levels of pip92 mRNA were detected in the hippocampal dentate gyrus and piriform cortex regions [11].
• The immediate early gene pip92 has been identified in serum-stimulated BALB/c 3T3 fibroblasts, activated T lymphocytes treated with cycloheximide, and fibroblast growth factor-stimulated hippocampal cells during neuronal differentiation [11].

Associations of Ier2 with chemical compounds

• The distribution of pip92 mRNA levels in the NMDA-treated mouse brain was investigated using in situ RT-PCR [11].
• The predicted open reading frame encodes a 308-amino-acid, highly proline-rich protein with homology to the amino terminus of the immediate-early gene pip92/Ier2/ETR101 [12].
• We report here that immediate early gene pip92 is expressed during anisomycin-induced cell death in fibroblast NIH3T3 cells [10].

Regulatory relationships of Ier2

• Further analysis of the SRE using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required for anisomycin-induced pip92 expression [10].

Other interactions of Ier2

• Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein [13].
• Genomic structure, cDNA sequence, and expression of gly96, a growth factor-inducible immediate-early gene encoding a short-lived glycosylated protein [14].
• Overall, this study suggested that different MAPK pathways are involved in the expression of immediate early gene pip92 by growth factors and environmental stresses [10].
• We have examined the expression of c-jun, one of the growth-factor-inducible immediate-early genes, during myogenic differentiation of L6 myoblasts [15].
• We also show that for two immediate-early genes, pip92 and nur77, formation of the ternary complex may occur without the prior assembly of SRF-DNA binary complex [16].

Analytical, diagnostic and therapeutic context of Ier2

• In this study we have demonstrated that pip92 is expressed in the mouse brain after a single intraperitoneal injection of NMDA [11].

References