GENE PROFILING, P53 STORY

P53
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At least half of the Sarcomas will show activity at P53, the cellular Molecule of the year in 1993,
in up to 10% of cases, the P53 will actually be mutated. It is either overexpressed or suppressed in the rest of the cases of Sarcoma.  The P53 is suppressed if repression occurs at P14 or at CDKN2A or if MDM2 is overexpressed.  P14 shield P53 from the effect of MDM2.  P53 is also overexpressed if its degradation is stopped at the proteasome.

At the nuclear level, Acetylated P53 combines to P300 and promote P21 and Puma leading to Apoptosis.  This effect can be blocked by Fusion protein  EWS-Fli1 in Ewing Sarcoma, and by upregulation of Histone DE-Acelase 1 which effectively blocks down transcription effect of P53.

If you count right, there are 6 potential targets of interaction with P53, if you include upstream toward the membranes...calling for Multitarget therapy in those conditions where wild type P53 is overexpressed!

GENE PROFILING IS A MUST STEP IN CANCER TREATMENT!

LOOPHOLE EXISTS WHEN p53 IS BLOCKED DOWNSTREAM THOUGH,
BLOCKAGE OF p53 IN THE NUCLEAR, TRIGGERS EXPRESSION OF JAG1, HEY1 WHICH INTENSIFY NOTCH3 AND STILL LEAD TO CELL CYCLE ARREST.