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The effect of cycloheximide on the expression of cell cycle dependent genes
Abstract:
We have investigated the inducibility of several cell cycle-dependent genes (plus control sequences, not expressed in a cell cycle-dependent manner) in the presence of cycloheximide, an inhibitor of protein synthesis. The genes studied include: 1) five cDNA clones that are preferentially expressed in the G1 phase of the cell cycle: KC-1, JE-3, 2F1, 4F1 and 2A9; 2) one gene preferentially expressed in late G1/S phase: histone H3; and 3) the cell cycle-dependent oncogene p53. All the genes studied are induced by serum even in the presence of cycloheximide. Previous results in the literature have shown that 2 other oncogenes, c-myc and c-fos, can be induced by growth factors in the presence of cycloheximide. Together with our results, these findings indicate that protein synthesis is not required for the induction of at least nine cell cycle genes by growth factors.
Insights
Protein synthesis is not required for growth factor-induced cell cycle gene activation. This study shows that key cell cycle genes, including oncogenes like p53, are induced by serum even when protein synthesis is blocked.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cell cycle progression is regulated by specific genes.
- Growth factors typically induce cell cycle gene expression.
- The role of protein synthesis in this induction is not fully understood.
Purpose of the Study:
- To investigate the inducibility of cell cycle-dependent genes in the presence of cycloheximide.
- To determine if protein synthesis is necessary for the induction of these genes by serum.
Main Methods:
- Treatment of cells with cycloheximide, a protein synthesis inhibitor.
- Analysis of the expression levels of specific cell cycle genes (KC-1, JE-3, 2F1, 4F1, 2A9, histone H3, p53) after serum stimulation.
- Comparison with previously reported findings on c-myc and c-fos gene induction.
Main Results:
- Five G1-phase specific cDNA clones (KC-1, JE-3, 2F1, 4F1, 2A9) were induced by serum despite cycloheximide treatment.
- Histone H3 (late G1/S phase) and the oncogene p53 were also induced by serum in the presence of cycloheximide.
- These findings align with literature showing c-myc and c-fos induction under similar conditions.
Conclusions:
- Protein synthesis is not a prerequisite for the serum-induced expression of at least nine cell cycle-associated genes.
- Growth factor signaling pathways can activate gene transcription independently of immediate protein synthesis.
- This suggests alternative regulatory mechanisms controlling early cell cycle gene expression.