Phosphorylation of p53 on Key Serines Is Dispensable for Transcriptional Activation and Apoptosis

The p53 tumor suppressor is a key mediator of the cellular response to stress. Phosphorylation induced by multiple stress-activated kinases has been proposed to be essential for p53 stabilization, interaction with transcriptional co-activators, and activation of p53 target genes. However, genetic studies suggest that stress-activated phosphorylation may not be essential for p53 activation. We therefore investigated the role of p53 phosphorylation key and for p53 activation a We that not the phosphorylation of of the of and p53 induced by the and and and to p53 target and to We that p53 phosphorylation is not for activation of p53 target The p53 tumor suppressor is a key mediator of the cellular response to stress. Phosphorylation induced by multiple stress-activated kinases has been proposed to be essential for p53 stabilization, interaction with transcriptional co-activators, and activation of p53 target genes. However, genetic studies suggest that stress-activated phosphorylation may not be essential for p53 activation. We therefore investigated the role of p53 phosphorylation key and for p53 activation a We that not the phosphorylation of of the of and p53 induced by the and and and to p53 target and to We that p53 phosphorylation is not for activation of p53 target The tumor suppressor p53 is a that a of cellular to response to p53 the of of to that not p53 activation not for the by The is by a the p53 and tumor suppressor by transcriptional is for p53 and p53 that p53 and response to the interaction be to p53 to with for activation of target genes. p53 activation of p53 multiple by and and to that and to p53 phosphorylation has been and has been proposed to a role the and activation of the tumor studies been by the of that p53 and and and been to phosphorylation response to kinases been the to p53 phosphorylation the of and not the of p53 and been to a role the interaction the and phosphorylation the p53 and and studies to the that phosphorylation of p53 is a key for activation of the tumor suppressor response to cellular to proposed role of and of the p53 phosphorylation has been of However, of p53 phosphorylation is and of p53 is of for a tumor has been that phosphorylation the transcriptional of p53 of the of cellular response to of p53 a may be by to and interaction with of the transcriptional has been that and phosphorylation may the of p53 and phosphorylation has been to the interaction of p53 with transcriptional and phosphorylation of has been the activation of response has been to p53 and and transcriptional is phosphorylation of p53 suggest that p53 phosphorylation may role not of p53 of transcriptional the phosphorylation p53 been that and p53 not to studies with of suggest that not essential for p53 activation the of the and of the the p53 with and p53 to of p53 and activation of the p53 and and p53 by to not to p53 and not with of with of p53 that is of phosphorylation may for the role of p53 phosphorylation cellular that p53 induced by the is not key the of 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that that kinases to p53 We therefore induced p53 phosphorylation key and The has a to a a of p53 and with and with induced the phosphorylation of of p53 a phosphorylation and and and phosphorylation and phosphorylation of p53 the with and and the with that not with p53 activation. p53 for the of phosphorylation to p53 of p53 by not phosphorylation of key and with for and the of p53 and p53 by a of p53 Phosphorylation transcriptional is of for a tumor We therefore the of p53 to of the transcriptional activation of the We the p53 that the of p53 that to a a p53 and with a of of and for and p53 the with the the of p53 a with The of p53 a that the of p53 The of p53 induced by the induced by and with that induced by suggest that the of phosphorylation phosphorylation not the of p53 to response of p53 to is not by phosphorylation and with and for and the of p53 the that to by the p53 and to the of p53 by Phosphorylation the transcriptional of and p53 of and with of and for We the of p53 target and by p53 p53 for transcriptional and of the p53 a that a key role the is a p53 and the is a with of p53 a activation of The the of the the transcriptional of p53 the of the for and The of by the for and for and the of the The not transcriptional activation of of the that the activation of p53 target by is to of interaction of not the phosphorylation of and with the of and for and the of and by a of p53 target of to a of p53 and to the of p53 However, that p53 phosphorylation p53 activation by interaction and of the the p53 activation may a and to p53 and of not be We investigated by the of transcriptional activation of the and to of and studies that is the for p53 The that the of and with induced p53 target the is with of with p53 not the p53 and p53 that p53 phosphorylation key phosphorylation is for and activation of transcriptional of of p53 target not p53 and to and for the and the of and by and a activation to of and the of p53 phosphorylation to is for of tumor p53 phosphorylation key to be for transcriptional may a role of the tumor suppressor proposed of the of by p53 may activation of multiple not to a to a for We and with the of and the for and the of studies and and that is the for of with the and the of with and not not The with the of for of the of p53 induced with of and for and and not the p53 of by with and for and the the and that the the of with and is to and induced by and and of The the of and and and a of the that with the of the of the However, and with has been that p53 is is to and of We the of and the the p53 is to a the of of and of for the of and to not that the of the and of and to the of and a of the p53 has been by the p53 a of the of of a and a the of p53 a to of with p53 the to and to of with and for a response to with and not the to The of not by the that p53 response is to a for cellular is and the with and and and and for and the of and by the of and and with the for and the of induced the the the of the not with that a of the the with of and is induced by of the is the the is to that of the that p53 that is phosphorylation key is to with p53 with that induced by of p53 is not by phosphorylation and with of and for and the the to role of phosphorylation p53 activation and has been a of studies the However, the studies phosphorylation response to the is of to phosphorylation a for of the role of phosphorylation of p53 is for of p53 and the of p53 with that of p53 the cellular that p53 is of the p53 to We that phosphorylation the is not for p53 activation. is with studies that p53 the of phosphorylation and p53 with induced by and However, by the of p53 induced by with not phosphorylation phosphorylation and the p53 p53 a of phosphorylation to the by The that p53 is not phosphorylation that be by is to that p53 by is of phosphorylation and p53 and to However, multiple and the activation of p53 target by been by that p53 with the that the phosphorylation not to p53 the that p53 is of is by not of p53 phosphorylation the transcriptional of p53 the that be the of p53 However, the a the of a to and p53 the p53 has been and the of the by p53 with p53 by that that phosphorylation is not for transcriptional activation of p53 target genes. 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of the with to with that to is to the that is the the p53 with and to the that p53 phosphorylation is not essential for of the p53 has for We that p53 and tumor of However, and not phosphorylation of p53 phosphorylation is for of transcriptional the of may be the of with p53 that of The tumor suppressor p53 is a that a of cellular to response to p53 the of of to that not p53 activation not for the by The is by a the p53 and tumor suppressor by transcriptional is for p53 and p53 that p53 and response to the interaction be to p53 to with for activation of target genes. p53 activation of p53 multiple by and and to that and to p53 phosphorylation has been and has been proposed to a role the and activation of the tumor studies been by the of that p53 and and and been to phosphorylation response to kinases been the to p53 phosphorylation the of and not the of p53 and been to a role the interaction the and phosphorylation the p53 and and studies to the that phosphorylation of p53 is a key for activation of the tumor suppressor response to cellular stress. to proposed role of and of the p53 phosphorylation has been of However, of p53 phosphorylation is and of p53 is of for a tumor has been that phosphorylation the transcriptional of p53 of the of cellular response to of p53 a may be by to and interaction with of the transcriptional has been that and phosphorylation may the of p53 and phosphorylation has been to the interaction of p53 with transcriptional and phosphorylation of has been the activation of response has been to p53 and and transcriptional is phosphorylation of p53 suggest that p53 phosphorylation may role not of p53 of transcriptional the phosphorylation p53 been that and p53 not to studies with of suggest that not essential for p53 activation the of the and of the the p53 with and p53 to of p53 and activation of the p53 and and p53 by to not to p53 and not with of with of p53 that is of phosphorylation may for the role of p53 phosphorylation cellular that p53 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phosphorylation a response to is with the that and not the kinases that p53 However, is that that kinases to p53 We therefore induced p53 phosphorylation key and The has a to a a of p53 and with and with induced the phosphorylation of of p53 a phosphorylation and and and phosphorylation and phosphorylation of p53 the with and and the with that not with p53 activation. p53 for the of phosphorylation to p53 of p53 Phosphorylation transcriptional is of for a tumor We therefore the of p53 to of the transcriptional activation of the We the p53 that the of p53 that to a a p53 and with a of of and for and p53 the with the the of p53 a with The of p53 a that the of p53 The of p53 induced by the induced by and with that induced by suggest that the of phosphorylation phosphorylation not the of p53 to response of p53 by Phosphorylation the transcriptional of and p53 of and with of and for We the of p53 target and by p53 p53 for transcriptional and of the p53 a that a key role the is a p53 and the 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