Molecular cloning and biological activity of a novel developmentally regulated gene encoding a protein with beta-transducin-like structure

• Published in: The Journal of biological chemistry 1994-04, Vol.269 (15), p.11318-11326
• Main Authors: SHARAD KUMAR, MATSUZAKI, T, YOSHIDA, Y, NODA, M
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding and carrier proteins; Biological and medical sciences; Brain - embryology; Brain - metabolism; Cattle; Cell Division; Cell Line; Cells, Cultured; Cloning, Molecular; DNA Primers; Embryo, Mammalian; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation; Genes. Genome; Gestational Age; GTP-Binding Protein beta Subunits; GTP-Binding Proteins - biosynthesis; GTP-Binding Proteins - genetics; GTP-Binding Proteins - physiology; Heterotrimeric GTP-Binding Proteins; Humans; Mice; Mice, Inbred ICR; Microtubule-Associated Proteins; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; PC12 Cells; Polymerase Chain Reaction; Proteins; Rats; Sequence Homology, Amino Acid; Suppression, Genetic; Transducin - biosynthesis; Transducin - genetics; Transducin - physiology; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)78128-9

In the developing mammalian central nervous system, neural precursor cells show a tightly regulated inverse relationship between cell proliferation and differentiation. The molecular mechanisms which control the inter-relationship between these two events are poorly understood. To approach this problem, we previously identified several novel genes which are most prominently expressed in the early embryonic brain. Further cloning and sequencing of one such gene, Nedd1, revealed that it can encode a protein with a M(r) of 71,000, the amino-terminal half of which shares significant structural similarity with the beta-subunit of heterotrimeric GTP-binding proteins. Nedd1 mRNA is strongly expressed in early embryonic brain, but it can be detected at low levels in a number of adult tissues as well as cell lines and is up-regulated in an embryonal carcinoma cell line upon retinoic acid-induced differentiation. Ectopic expression of Nedd1 gene by means of eukaryotic vectors in various cell lines resulted in varying degrees of growth suppression. The strongest effects were evident in differentiation-competent neuroblastoma-derived cell lines. Our results suggest that the Nedd1 gene may play a role in the differentiation-coupled growth arrest in neuronal cells.