MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity

The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and activation, leading to G1arrest

“…Several studies indicate that sumoylation of p53 may promote its transcription factor activity, while others have reported that sumoylation represses transcription. 28,[32][33][34] Results may potentially be reconciled by the recent finding that phosphorylation or acetylation of SUMO-1 may occur to regulate whether sumoylation can be inhibitory or stimulatory. 36 Thus, sumoylation of p53 may have either an inhibitory or activator function, depending upon whether SUMO-1 has been acetylated and the promoter context or cell type studied.…”

“…The p53 tumor suppressor protein is subject to many post-translational modifications, including phosphorylation, acetylation, modification with ubiquitin and related proteins, such as SUMO and NEDD8. [25][26][27][28] These modifications regulate p53 at a number of levels, including control of protein turnover, subcellular localization and changes in the ability to regulate gene expression.…”

Brg1 regulates the transcription of human papillomavirus type 18 E6 and E7 genes

“…40 In normal cells, the major regulator of p53 is Mdm2 which is both a ubiquitin-E3-ligase dictating the polyubiquitination and degradation of p53 38 and a SUMO-E3-ligase conferring p53 sumoylation to modulate its transcriptional activity. 41 Mdm2 overexpression is seen in many solid tumors, which, in some cases, is associated with certain type of single nucleotide polymorphism (SNP) in Mdm2 promoter. 42 The elevated expression of Mdm2 is able to destabilize p53, disturb the p53 function and thus SNP in Mdm2 promoter relates to tumorigenesis.…”

Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

“…This mechanism would effectively impair any inhibitory modification of p53 by Mdm2, which includes not only ubiquitylation, but also neddylation 51 and sumoylation. 52 Future studies examining the effects of NIAM on those alternative lysine modifications of p53 are warranted. Notably, our data are not consistent with Tip60 binding to NIAM-Mdm2 complexes, since Tip60 and NIAM influence p53 stability through different mechanisms.…”