Cloning and functional studies of a novel gene aberrantly expressed in RB-deficient embryos

Shyng Shiou F. Yuan, Laura A. Cox, Gopal K. Dasika, Eva Y.H.P. Lee

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    92 Scopus citations

    Abstract

    The tumor suppressor RB regulates diverse cellular processes such as G1/S transition, cell differentiation, and cell survival. Indeed, Rb-knockout mice exhibit phenotypes including ectopic mitosis, defective differentiation, and extensive apoptosis in the neurons. Using differential display, a novel gene, Rig-1, was isolated based on its elevated expression in the hindbrain and spinal cord of Rb-knockout embryos. The longest open reading frame of Rig-1 encoded a polypeptide that consists of a putative extracellular segment with five immunoglobulin-like domains and three fibronectin III-like domains, a putative transmembrane domain, and a distinct intracellular segment. The Rig-1 sequence was 40% identical to the recently identified roundabout protein. Consistent with the predicted transmembrane nature of the protein, Rig-1 protein was present in the membranous fraction. Antisera raised against the putative extracellular and intracellular segments of Rig-1 reacted with an ~210-kDa protein in mouse embryonic CNS. Rig-1 mRNA was transiently expressed in the embryonic hindbrain and spinal cord. Elevated levels of Rig- 1 mRNA and protein were found in Rb(-/-) embryos. Ectopic expression of a transmembrane form of Rig-1, but not the secreted form, promoted neuronal cell entrance to S phase and repressed the expression of a marker of differentiated neuron, Tα1 tubulin. Thus Rig-1, a possible distant relative of roundabout, may mediate some of the pleiotropic roles of RB in the developing neurons.

    Original languageEnglish (US)
    Pages (from-to)62-75
    Number of pages14
    JournalDevelopmental Biology
    Volume207
    Issue number1
    DOIs
    StatePublished - Mar 1 1999

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    Keywords

    • Neuronal cell cycle control
    • Neuronal differentiation
    • RB
    • Transcriptional regulation

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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