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  • Title: Mitogenic up-regulation of the PRL-1 protein-tyrosine phosphatase gene by Egr-1. Egr-1 activation is an early event in liver regeneration.
    Author: Peng Y, Du K, Ramirez S, Diamond RH, Taub R.
    Journal: J Biol Chem; 1999 Feb 19; 274(8):4513-20. PubMed ID: 9988683.
    Abstract:
    The cellular signals that initiate cell growth are incompletely understood. Insight could be provided by understanding the signals regulating the transcriptional induction of immediate-early genes which occurs within minutes of the growth stimulus. The expression of the PRL-1 gene, which encodes a unique nuclear protein-tyrosine phosphatase, is rapidly induced in regenerating liver and mitogen-treated cells. Transcription of the PRL-1 gene increased in the rat liver remnant within a few minutes after partial hepatectomy and largely explained the increase in steady-state PRL-1 mRNA in the first few hours posthepatectomy. Egr-1 (early growth response factor) specifically bound a region of the proximal PRL-1 promoter P1 (-99). Egr-1 binding activity was more rapidly induced in regenerating liver than mitogen-treated H35 and NIH 3T3 cells, remained elevated through 4 h posthepatectomy, and appeared to be dependent not only on new Egr-1 protein synthesis but on post-translational regulation of Egr-1. Egr-1 efficiently transactivated a PRL-1 promoter reporter construct containing an intact not mutant Egr-1 site, and the Egr-1 site largely accounted for PRL-1 gene up-regulation in response to mitogen stimulation. These data predict that Egr-1 activation is an early event in liver regeneration and mitogen-activated cells that provides a regulatory stimulus for a subset of immediate-early genes.
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