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

Research output: Contribution to journalArticlepeer-review

98 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
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Cloning and functional studies of a novel gene aberrantly expressed in RB-deficient embryos'. Together they form a unique fingerprint.

Cite this