Mouse mammary tumor gene int-3: a member of the notch gene family transforms mammary epithelial cells.
Expression of a 2.3-kb RNA species is induced in mammary tumors as a consequence of insertional mutagenesis at the int-3 locus by the mouse mammary tumor virus. The nucleotide sequence and biological activity of this mammary tumor-specific int-3 RNA species were determined. It contains an open reading frame which encodes a 57-kDa protein. The translated protein possesses six nearly contiguous 32-amino-acid repeats which are related to a similar motif in the Saccharomyces cerevisiae cdc-10-encoded cell cycle protein. In addition, the int-3 cdc-10 repeats are bounded by the PEST amino acid sequence motif which is commonly found in proteins having a rapid turnover and may represent sites for phosphorylation. The int-3 cdc-10 repeat sequences are 50% identical to a portion of the intracellular domain of the neurogenic Drosophila notch gene product. Activation of expression of a recombinant int-3 genomic DNA fragment encoding the 2.3-kb RNA species in HC11 mouse mammary epithelial cells in vitro induces anchorage-independent growth in soft agar.
Robbins
J
J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892.
Blondel
B J
BJ
Gallahan
D
D
Callahan
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics*; D004279:DNA, Viral; D004847:Epithelial Cells; D007301:Insect Hormones / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000166:cytology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D016415:Sequence Alignment; D014158:Transcription, Genetic
D004279:DNA, Viral; D007301:Insect Hormones; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C073572:Notch4 protein, mouse