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Regulation of expression of growth arrest-specific genes in mouse fibroblasts
C Ciccarelli1, L Philipson, V Sorrentino
1European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Abstract:
The suppression of growth arrest-specific (gas) gene expression by serum appeared to be independent of protein synthesis, but expression in resting cells was sensitive to 2-aminopurine, an inhibitor of intracellular protein kinases. Although accumulation of gas gene mRNA was reduced by serum, nuclear transcription of the gas-2, -3, and -5 genes was observed in serum-stimulated cells, indicating that posttranscriptional events may regulate mRNA levels. Growth induction by serum, on the other hand, led to suppression of transcription of the gas-1 gene. Cell cycle regulation and the serum response of gas-1 were lost in ras-transformed cells.
Insights
Serum affects growth arrest-specific (gas) gene expression through posttranscriptional regulation and transcription suppression, with altered regulation in ras-transformed cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Gene Regulation
Background:
- Growth arrest-specific (gas) genes play a role in cell cycle regulation.
- Serum stimulation is a key factor influencing cellular responses, including gene expression.
Purpose of the Study:
- To investigate the regulatory mechanisms of growth arrest-specific (gas) gene expression by serum.
- To determine the role of protein synthesis, intracellular protein kinases, and transcriptional/posttranscriptional events in gas gene regulation.
- To examine the impact of ras transformation on gas gene regulation and serum response.
Main Methods:
- Treatment of cells with serum and 2-aminopurine.
- Analysis of gene expression, mRNA accumulation, and nuclear transcription.
- Comparison of gene regulation in normal and ras-transformed cells.
Main Results:
- Serum-induced suppression of gas gene expression was largely independent of protein synthesis but sensitive to protein kinase inhibition.
- Serum reduced gas gene mRNA accumulation, yet nuclear transcription of gas-2, -3, and -5 persisted, suggesting posttranscriptional regulation.
- Serum suppressed gas-1 gene transcription during growth induction.
- Ras transformation abolished cell cycle regulation and serum response of gas-1.
Conclusions:
- Posttranscriptional mechanisms significantly regulate gas gene mRNA levels in response to serum.
- Serum differentially regulates the transcription of gas genes, with suppression observed for gas-1.
- Ras transformation disrupts normal cellular responses to serum, affecting gas gene regulation.