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.
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.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.forename: K
authors.initials: K
authors.lastname: Du
authors.forename: S
authors.initials: S
authors.lastname: Ramirez
authors.forename: R H
authors.initials: RH
authors.lastname: Diamond
authors.forename: R
authors.initials: R
authors.lastname: Taub
mesh_terms: D016475:3T3 Cells; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008115:Liver Regeneration; D008565:Membrane Proteins; D051379:Mice; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation