Adenovirus disrupts cancer cells !!!! or they HOPE

Salk Institute for Biological Studies:

Ok, so we know that our precious p53 (which is a tumor suppressor protein) is involved in preventing cancer. So p53 generally eliminates abnormal cells from the body ( or any virus-infected cells). Similar to tumor cells adenoviruses (main cause of upper respiratory infections) multiply better when p53 is not around.

According to Dr. O'Shea, adenoviruses do not inactivate p53 directly. Instead, they target the genome itself. Adenovirus brings in E1B-55K (a protein encoded by the E1B genomic region of Adenovirus), which binds to and degrades p53... and thus inhibiting apoptosis in the infected cells. So if adenovirus didn't have E1B-55K, it wouldn't be able to inactivate p53, and would only be able to replicated in tumor cells that are p53-deficient. So then, each time it ruptures the host cell to release viral progenies, the next generation of viruses leave normal cells unharmed while seeking out the remaining cancer cells. And According to Dr. O'Shea,

"This makes adenovirus a perfect candidate for oncolytic cancer therapy."

Dr. Conrado Soria, notes that "the inability of the E1B-55K-mutant virus to replicate in normal cells was not because the virus failed to degrade p53."

Due to rapid degradation, p53 is found to be at low levels in normal and unstressed cells. However, if there is DNA damage, activation of oncogenes or infection, degradation of p53 is stopped and thus its levels accumulate. This accumulation stop the cell cycle or induce apoptosis by activating p53 target genes. As Dr. Soria predicted, normal cells that had been infected with adenovirus that LACKED E1B-55K, p53 accumulated but target genes were still able to be turned on ... making apoptosis possible. This is because of another protein in the adenovirus ! YAY ! The E4-ORF3 ... this protein is a beast ! It modifies chromatin, so that parts of chromosomes condenses into heterochromatin, so that the regulatory regions of p53 target genes somewhere thats inaccessible. Therefore, the tumor suppressor cant bind to its target genes anymore, p53 becomes useless and apoptosis no longer occurs.

What does all this mean? it means that Dr. O'Shea "HOPES" to understand how high levels of wild type p53 may be inactivated in cancer ! He says, "our study really changes the longstanding definition of how p53 is inactivated in adenovirus-infected cells and will finally allow us to develop true p53 tumor selective oncolytic therapies."