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2017 ; 9
(1
): 62-68
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Negative auto-regulators trap p53 in their web
#MMPMID28069666
Zhou X
; Cao B
; Lu H
J Mol Cell Biol
2017[Feb]; 9
(1
): 62-68
PMID28069666
show ga
The transcriptional factor p53 activates the expression of a myriad of target
genes involving a complicated signalling network, resulting in various cellular
outcomes, such as growth arrest, senescence, apoptosis, and metabolic changes,
and leading to consequent suppression of tumour growth and progression. Because
of the profoundly adverse effect of p53 on growth and proliferation of cancer
cells, several feedback mechanisms have been employed by the cells to constrain
p53 activity. Two major antagonists MDM2 and MDMX (the long forms) are
transcriptionally induced by p53, but in return block p53 activity, forming a
negative feedback circuit and rendering chemoresistance of several cancer cells.
However, they are not alone, as cancer cells also employ other proteins encoded
by p53 target genes to inhibit p53 activity at transcriptional, translational,
and posttranslational levels. This essay is thus composed to review a recent
progress in understanding the mechanisms for how cancer cells hijack the p53
autoregulation by these proteins for their growth advantage and to discuss the
clinical implications of these autoregulatory loops.
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