Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells.
Purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin. Mutational analysis suggests that the GAGA box plays an important role in transcription of the rat insulin I gene. We identify here at least four different proteins that bind specifically to the insulin GAGA box. Using a GAGA oligonucleotide, we have isolated a cDNA encoding a sequence-specific protein from a HIT (hamster insulinoma cell line) lambda gt11 library. This protein, which we designate Pur-1 (for purine binding), binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Pur-1 is a potent transactivator in both pancreatic and nonpancreatic cells. Furthermore, Pur-1 is able to activate an intact insulin promoter in HeLa cells, where it is normally inactive.
Kennedy
G C
GC
Hormone Research Institute, University of California, San Francisco 94143-0534.
Rutter
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D007328:Insulin; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein