Tuesday, October 24, 2017

p53

What about p53?

P53 is a transcription factor.  P53 would end a cancer cell if functional. (but it doesn't start the cancer) This is one of the most critical defense genes against cancer.

P53 regulates cell cycle and pushes cells from stem to differentiated
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001268
https://www.ncbi.nlm.nih.gov/pubmed/1614522

P53 review:  haulting growth, repair, apoptosis (so low levels are common)
http://www.bioinformatics.org/p53/introduction.html

50% of cancers have lost the P53 gene (mutation or inactivation)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756401/
http://www.nature.com/onc/journal/v26/n15/full/1210280a.html

The cancers with p53 may be the "chemo-resistant" cancers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756401/

In breast cancer the p53 mutation appears with the most aggressive forms
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr426

Triple negative Breast cancer and p53 mutations
https://www.futuremedicine.com/doi/abs/10.2217/bmt.13.59?journalCode=bmt

Methylation of p53 in ovarian cancer
https://www.ncbi.nlm.nih.gov/pubmed/22855178

methylation of p53 decreases its ability to arrest the cell cycle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762123/

The methylated version is with the slower cancers

In order for viruses to replicate in the nucleus they must control the P53....seems confusing

EBV (herpes virus) and P53
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754062/

SV40 (polyomavirus) inhibits P53 completely or mutates it
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1560412/
https://www.ncbi.nlm.nih.gov/pubmed/9129663

HPV (human papilloma virus)  inhibits P53
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC236349/

But in co-carcinogenesis the virus polymerase has been bound by the carcinogen and the viral proteins are not made. 

But there is a difference between viruses. Some infect using receptors that methylate DNA while others use receptors that would demethylate.

Herpes viruses which are connected to estrogen receptors methylate.
HPVs which are connected to cannabinoid receptors demethylate.

EBV has been associated with Ovarian and estrogen positive breast cancer.
HPV has been associated with TNBC and cervical.

P53, HPV, and cervical cancer
https://www.ncbi.nlm.nih.gov/pubmed/21672450








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