P53 PRIMA-1 paper
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who are the authors of this paper and when was it published?
Lambert et al 2009
What does the restoration of WT P53 expression trigger in vivo?
It triggers cell death and eliminates tumours in vivo
give an exampl of a mutant P53 reactivating small molecule?
PRIMA-1
How does PRIMA-1 effect mutant P53?
PRIMA-1 converted to compounds that forms adducts with thiols in mutant P53 - this covalent modification of mutant P53 by PRIMA-1 is sufficient to induce apoptosis in tumour cells.
what kind of protein is P53 and when does it become activated?
P53 is a TRANSCRIPTION FACTOR - becomes activated in response to cellular stress
what happens when P53 transciption occurs?
Cell cycle arrest, senescence and apoptosis occurs.
what is meant by senescence of a cell?
loss of a cells power to divide and grow
does a P53 increase the resistance to chemotherapy?
possibly
how were small molecules identified which reactivated mutant P53?
Screening studies
which small molecules induce many P53 target genes and P53 dependent apoptosis?
PRIMA-1 and PRIMA1met
what happens when there is systemic administration of PRIMA1 or PRIMA1met into mice?
It inhibits xenograft tumour growth in mice
What does PRIMA1met synergise with?
PRIMA1met synergises with chemotherapy drugs to induce tumour cell apoptosis
what is meant by synergy?
the interaction/coorperation of two agents to produce a combined effect which is greater than the sum of their individual effects.