Proceedings of the National Academy of Sciences · 1988 · 537 citations · 47 references
Life SciencesGeneticsMolecular BiologyCell ProliferationGene ExpressionTranscriptional RegulationGrowth Factor SignalingHormone Binding ProteinsHormone ReceptorsHormone SignalingNuclear ReceptorsSteroid Hormone SignalingCdna CloningG1 TransitionG1-s Phase TransitionG1/s TransitionGrowth FactorsImmediate Early Gene ExpressionImmediate Early GenesThyroid Hormone Receptors
Genes expressed during the G0/G1 transition in mouse fibroblasts were identified by cDNA cloning. The immediate‑early gene nur/77, induced by serum or growth factors, encodes a 601‑amino‑acid ligand‑binding nuclear receptor that likely regulates the genomic response to growth factors.
We previously identified, by cDNA cloning, a set of genes that are expressed during the G0/G1 transition (cell cycle reentry) in mouse fibroblasts. These immediate early genes are transcriptionally activated within minutes of addition of serum or purified growth factors, and their mRNAs are superinduced in the presence of protein-synthesis inhibitors. We report here that one of these genes, represented by nur/77 cDNA (originally called 3CH77), encodes a member of the superfamily of ligand-binding transcription factors that includes the steroid and thyroid hormone receptors. The nur/77 cDNA sequence encodes a protein of 601 amino acids containing two regions of sequence similarity to members of this nuclear receptor superfamily, corresponding to their DNA-binding and ligand-binding domains. These results suggest that the growth factor-inducible immediate early gene nur/77 encodes a ligand-binding protein that regulates the genomic response to growth factors.
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