Transcriptional regulation of IER3IP1 gene by tumor necrosis factor-alpha and Sp family proteins.

Immediate early response 3 interacting protein 1 (IER3IP1) is an endoplasmic reticulum protein with its potential cellular function involved in cell differentiation and cell death processes. In this report, we investigated the molecular mechanism by which the expression of IER3IP1 gene is regulated by cloning the 5' flanking region of the human IER3IP1 gene for various promoter studies. Deletion analysis was used to identify the basal promoter activity retained at -298/-59 region and mutation analysis proved that Sp1 is a transcriptional activator of this gene expression. As an early response gene, IER3IP1 showed an increase in transcription in response to tumor necrosis factor alpha (TNF-alpha) in a time- and dose-dependent manner. This inducible response to TNF-alpha is mediated by the demonstration of nuclear factor kappaB (NF-kappaB) responsive element on IER3IP1 promoter sequence. From our results, we suggest that IER3IP1 gene is involved in TNF-alpha-mediated cellular response to stressful conditions.

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