Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines.
The human homologue of Drosophila tumor suppressor dlg, hDLG1, is one of the proteins known to interact with APC, a tumor suppressor for colorectal cancer. Alternative splicing of this gene generates transcripts either with [insertion 1 (I1)] or without 99 nucleotides in the 5' part of the dlg homology repeats (DHR) domain. We found almost equivalent expression of these two splicing variants in most human tissues; however, in skeletal muscle the transcript with the 99-bp insertion was predominant, and in the brain, that without the 99-bp insertion was expressed predominantly. We also examined alternative splicing in the region between the SH3 and GUK domains where two different sizes of insertions, 34 nucleotides (I2) or 100 nucleotides (I3), had been reported, and found various splicing patterns among the tissues examined. In brain we detected six different, alternatively spliced transcripts, two of which included a novel, 36-bp, brain-specific exon encoding a peptide bearing significant homology to a portion of rat synapse-associated protein, SAP97/PSD95. Subsequently, we investigated the splicing patterns of the hDLG1 gene in 24 neuroblastoma cell lines. In two-thirds of these lines, the splicing patterns were altered from those observed in normal brain tissue. As one-third retained the normal brain-splicing pattern, the loss of normal splicing of hDLG1 may not in itself cause formation of tumors, but it might reflect the biological character of individual neuroblastomas.
Mori
K
K
Department of Medical Genetics, Osaka University Medical School, Japan.
Iwao
K
K
Miyoshi
Y
Y
Nakagawara
A
A
Kofu
K
K
Akiyama
T
T
Arita
N
N
Hayakawa
T
T
Nakamura
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C501119:Dlg1 protein, rat; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila