Hi Frank,

It's been a while since I've worked on p53 but if I recall then cancer cells can upregulate the negative regulator MDM2 (which binds p53, thereby rendering it inactive). Thus, you have wild type p53 but still no activity. Have a look, I think Wikipedia actually explains parts of that. And second, even though p53 is mutated in very many cancer lines, there are many more proteins that can render a cell malignant without p53 being affected. Examples would be myc, RAS, different growth factors, other apoptosis regulators apart from p53, and literally dozens of other proteins, so-called oncogenes or proto-oncogenes. Also, normally more than one gene is affected before a cell turns malignant.

Hope that helps!

Hello

Loss of p53 function contributes to tumor progression through a combination of increased genetic instability, loss of growth-arresting signals, addition to oncogene .

Look at links here hope help you .

http://www.cell.com/cell/fulltext/S0092-8674(07)00246-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756401/

Article Understanding wild-type and mutant p53 activities in human c...

Article Tumor suppressor p53: Analysis of wild-type and mutant p53 complexes

Good Luck

The simple answer is P53 is not a direct supressor of its target genes. It is an activator of P21 WAF1/CIP (main mechanism, by stabilising the transcription promotion suppressiong DREAM complex), mdm2 and bbc3. If these genes, expecially p21 are mutated or suppressed in any other way, p53 wt does have at least less or no effect.

Methylation plays one of major roles to repress wild type p53 activity in cancer cells.

For example, Lysine methylation represses p53 activity in teratocarcinoma cancer cells. (PANS, 2016)

Thanks.

Hope this article help you.

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