Question

What is common among biological processes that are downregulated in p53-bound promoters upon doxorubicin treatment of mouse embryonic fibroblasts?

Answer 1

Doxorubicin is an anthracycline DNA intercalator anticancer drugs [which causes DNA double-strand breaks in rapidly dividing cells,

p53 presented as bound to enhancers at promter regions in healthy fibroblasts and is programmed for rapid activation in response to DNA damage. Upon DNA damage , it becomes activated and play an important role in regulation of cell cycle, genomic stability and apoptosis.

Among the activation of p53 , it downregulte or decrese the cell Gq to S transition so provide cell enough time to repair the damage.

P53 activate p21 protein , this p21 protein binds with cyclin - CDK complex thus interfere at check points and halt the cell. It jokes for cell long enough that the DNA repair will have enough time to perform their work.

p53 has a tissue-level anticancer effet by inhibiting angiogenesis. As tumors required  new blood vessels to supply them nutrients during growth, and p53 inhibits angiogenesis by (i) interfering with regulators of humor hypoxia that also affect angiogenesis, such as HIF1 and HIF2, (ii) inhibiting production of angiogenic promoting factors, and (iii) directly increasing the production of angiogenesis inhibitors, such as arresten.