"We next investigated if inhibition of lincRNA-p21, which affected interactions between p300, MDM2, and p53 proteins without altering p53 protein level, influenced p53 binding to the promoters/enhancers of its target genes."
"In fact, single mutation of Ser15 or Ser20 to alanine on full-length p53 has been shown to affect p53-dependent processes in transcription and apoptotic assays, p53-protein stability assays, and in th[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53."
"In anoxia, p53 competitively binds to p300 and Mdm2 targets HIF-1α for degradation; thus, the HIF-1α ac level drops markedly, and rather low levels of p21 are induced."
"It is likely that, similar to p53-MDM2 and p53-p300 interactions, the p53-KLF4 interaction is also affected by these mutations, contributing to the loss of transactivation of cell-cycle arrest genes."
"These observations suggest that lincRNA-p21, a transcriptional target of p53, can feed back and regulate the activity of p53, at least in part, by modulating the interaction of p53, p300 and MDM2."
"To understand how the lincRNA-p21 and MDM2 interaction affects the formation of the p53, p300, and MDM2 complex, co-immunoprecipitation (Co-IP) experiments were performed."
"Mutated TP53 residues 18 and 27 interact with both MDM2 and EP300 ( xref )."
"First, the work of Grossman and colleagues suggested that degradation of p53 by HDM2 is linked to the formation of a multimeric complex containing p53, p300, and HDM2  ."
"However, the binding of p53 with TAg also increases the half-life and steady-state levels of p53 in cell culture partly due to the entrapment of the p300, mdm2, and p53 complex that targets p53 for degradation."
"In addition, p300 interacts with both p53 and MDM2 through domains distinct from those involved in transcriptional coactivation  ."
"p300 interacts, specifically and independently, with both p53 and MDM2, and these interactions are required for normal p53 turnover."
"Clearly, this dynamic interaction between p300, MDM2, and p53 critically regulates the activity and function of p53, and positions MDM2 as a core regulator of p53 activity xref , xref , xref ."
"More recently, the association of p53 and MDM2 in chromatin was found to correlate with repression of transcription, whereas the absence of association of p53 and MDM2 in chromatin correlated with activation of transcription ( xref ), suggesting that functional association of MDM2 or p300 with p53 is mutually exclusive."
"Alternatively, these viral oncoproteins may also interfere with the binding of p300 and MDM2, a negative regulator of p53, also shown to bind to the CH1 domain of p300 ( xref )."
"Phosphorylated MDM2 interacts with p300 and p53, which undergoes ubiquitination, and degradation of p53 ( xref )."
"Also, binding of MDM2 to the p300-p53 complex blocked p300-mediated acetylation and activation of p53 ( xref )."
"These results indicate that the MDM2, p300, and p53 complex is intimately involved in p53 turnover, acetylation, and activation."
"Taken together, these observations strongly suggest that binding of endogenous p300 to native p53 and MDM2 through the C/H1 region contributes to normal MDM2-mediated p53 turnover in at least some cel[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"Experiments to determine how ARF affects the complex interaction of p53, MDM2 and p300 are underway."
"Hence, if p53 TAD anchors additional binding sites for σ and τ that are created upon DNA damage, it is possible that binding of σ and τ to p53 TAD could competitively inhibit the binding of MDM2 to p53 TAD, resulting in increased p53 levels, similar to competitive binding of p300 and MDM2 to p53 TAD ( xref )."
"We confirmed the interaction of p300 and p53, and MDM2 and p53, consistent with prior reports xref - xref ."