Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein.
We have cloned a cDNA for a novel human homolog of the Drosophila discs large (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig). Northern blot analysis revealed that the gene is highly expressed in neuronal and endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE-dlg antibody showed that the protein tended to be expressed in non-proliferating cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of the heart muscles, and the prickle and functional layer cells of the esophageal epithelium. Proliferative cells, including various cultured cancer cell lines and basal cells in the esophageal epithelium, showed little expression of the NE-dlg protein. In addition, yeast two-hybrid screening and in vitro binding assays revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC tumor suppressor protein. These data suggest that NE-dlg negatively regulates cell proliferation through its interaction with the APC protein.
Makino
K
K
Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Honjo Kumamoto, Japan.
Kuwahara
H
H
Masuko
N
N
Nishiyama
Y
Y
Morisaki
T
T
Sasaki
J
J
Nakao
M
M
Kuwano
A
A
Nakata
M
M
Ushio
Y
Y
Saya
H
H
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics*; D000074288:Discs Large Homolog 1 Protein; D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019476:Insect Proteins / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014960:X Chromosome / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; C513314:DLG1 protein, human; C116869:DLG3 protein, human; D018076:DNA, Complementary; D000074288:Discs Large Homolog 1 Protein; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila