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Fos family members induce cell cycle entry by activating cyclin D1
1Division of Neuroscience, Children's Hospital, Boston, Massachusetts 02115, USA.
Abstract:
Expression of the fos family of transcription factors is stimulated by growth factors that induce quiescent cells to reenter the cell cycle, but the cellular targets of the Fos family that regulate cell cycle reentry have not been identified. To address this issue, mice that lack two members of the fos family, c-fos and fosB, were derived. The fosB-/- c-fos-/- mice are similar in phenotype to c-fos-/- mice but are 30% smaller. This decrease in size is consistent with an abnormality in cell proliferation. Fibroblasts derived from fosB-/- c-fos-/- mice were found to have a defect in proliferation that results at least in part from a failure to induce cyclin D1 following serum-stimulated cell cycle reentry. Although definitive evidence that c-Fos and FosB directly induce cyclin D1 transcription will require further analysis, these findings raise the possibility that c-Fos and FosB are either direct or indirect transcriptional regulators of the cyclin D1 gene and may function as a critical link between serum stimulation and cell cycle progression.
Insights
Mice lacking c-fos and fosB genes show reduced size and impaired cell proliferation. These mice fail to induce cyclin D1, suggesting Fos proteins regulate cell cycle reentry.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Growth factors stimulate quiescent cells to reenter the cell cycle.
- The Fos family of transcription factors is involved in this process.
- Cellular targets of Fos proteins regulating cell cycle reentry remain unidentified.
Purpose of the Study:
- To investigate the role of c-Fos and FosB in cell cycle reentry.
- To identify potential cellular targets of the Fos family involved in proliferation.
Main Methods:
- Generation of mice lacking both c-fos and fosB genes (fosB-/- c-fos-/-).
- Phenotypic analysis of the knockout mice.
- Proliferation assays on fibroblasts derived from knockout mice.
- Analysis of cyclin D1 induction following serum stimulation.
Main Results:
- fosB-/- c-fos-/- mice exhibit a smaller size (30% reduction) compared to controls, indicating a cell proliferation defect.
- Fibroblasts from these mice show impaired proliferation.
- A key finding is the failure to induce cyclin D1 in response to serum stimulation in these cells.
Conclusions:
- c-Fos and FosB may act as transcriptional regulators of the cyclin D1 gene.
- These transcription factors could be critical for linking serum stimulation to cell cycle progression.
- The study highlights a potential mechanism by which Fos proteins control cell proliferation.