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J Biol Chem, Vol. 273, Issue 27, 17286-17295, July 3, 1998

The Gene Encoding Human Nuclear Protein Tyrosine Phosphatase, PRL-1
CLONING, CHROMOSOMAL LOCALIZATION, AND IDENTIFICATION OF AN INTRON ENHANCER

Yong Peng, Anna Genin^§, Nancy B. Spinner^§, Robert H. Diamond^¶, and Rebecca Taub

From the  Department of Genetics and the ^§ Department of Pediatrics, Division of Genetics, Children's Hospital of Philadelphia and the ^¶ Department of Medicine and Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Expression of the rat PRL-1 gene, which encodes a unique nuclear protein tyrosine phosphatase, is positively associated with cellular growth during liver development, regeneration, and oncogenesis but with differentiation in intestine and other tissues. Here, we analyzed the structure of the human PRL-1 gene and localized it to chromosome 6 within band q12. Human, rat, and mouse PRL-1 are 100% conserved at the amino acid level and 55% identical to a newly identified Caenorhabditis elegans PRL-1. The presence of two promoter activities, P1 and P2, in the human PRL-1 gene were identified by primer extension and RNase protection assays. A functional TATA box was identified in promoter P1 upstream of the non-coding first exon. A non-canonical internal promoter, P2, was found in the first intron that results in PRL-1 transcripts beginning 8 base pairs downstream of the 5'-end of exon 2 and causes no alteration in the encoded protein. The first 200-base pair region of either promoter P1 or P2 conferred high basal transcriptional activity. An enhancer that bound a developmentally regulated factor, PRL-1 intron enhancer complex (PIEC), was localized to the first intron of the human PRL-1 gene. The presence of PIEC correlated with the ability of the intron enhancer to confer transcriptional activation in HepG2 and F9 cells. The intron enhancer contributed significantly to PRL-1 promoter activity in HepG2 cells which contain PIEC but not to NIH 3T3 cells which do not.

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