wild-type p53 in cancer - (Oct/03/2006 )

hi all,

Mutation in p53 is often found in cancer patients but not all cancer patients have the mutated p53. If the patient's p53 protein is still working (no mutation), then shouldnt the cell cycle be arrested in G1 phase or subjected to apoptosis? Why does the patient still develop cancer?

Thank you!

There are p53-regulating proteins like MDM2, that when amplified will prevent WT p53 activation.

Mdm2 is able to bind, ubiquitinate and shuttle p53 to the cytoplasm. This leads to the degradation of p53 by the proteasome (some groups published there are proteasomes in the nucleus as well as in the cytoplasm).
There is another protein involved in Mdm2-mediated p53 regulation: p14ARF.
ARF can block the shuttling between nucleus and cytoplasm of the Mdm2-p53 complex or even inhibit the complex formation (Sherr, 1998; Sherr and Weber, 2000). If you have a deletion or a methilation of ARF, Mdm2 action will not be inhibited and p53 protein levels and activity will be downregulated. This is only the tip...
I would advice you to read some reviews about it