4 Chapter : Discussion
4.6 ummar and conclusions
This project sought to explore the mechanism of how ACL and its metabolic product, acetyl-CoA, can regulate the cell cycle of myeloid progenitor cells. We
hypothesized that inhibiting ACL function with the drug, BMS303141, would cause cell cycle arrest in myeloid progenitor cells (iBN cells), and that acetyl-CoA supplementation would be able to rescue the cell cycle. The evidence presented in this project supports our hypothesis. We have been able to demonstrate that ACL inhibition via BMS treatment causes cell cycle arrest and that acetyl-CoA supplementation is able to restore the cell cycle. We have also demonstrated novel evidence that acetyl-CoA can enter cells and that acetyl-CoA is incorporated into both lipids and histones for acetylation. Following BMS treatment, we have demonstrated that acetyl-CoA incorporation in lipids increases
suggesting that lipid biosynthesis is the pathway responsible for rescuing cell cycle arrest following BMS treatment. Whether histone acetylation also increases remains to be confirmed. In conclusion, we have shown that ACL inhibition is sufficient to cause cell cycle arrest, but acetyl-CoA supplementation is able to rescue the cell cycle through both lipid biosynthesis and histone acetylation pathways.
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