description
TP53 (p53) tumor suppressor protein is a transcription factor that functions as a homotetramer (Jeffrey et al. 1995). The protein levels of TP53 are low in unstressed cells due to MDM2-mediated ubiquitination that triggers proteasome-mediated degradation of TP53 (Wu et al. 1993). The E3 ubiquitin ligase MDM2 functions as a homodimer/homo-oligomer or a heterodimer/hetero-oligomer with MDM4 (MDMX) (Linares et al. 2003, Toledo and Wahl 2007, Cheng et al. 2011, Wade et al. 2013).Activating phosphorylation of TP53 at serine residues S15 and S20 in response to genotoxic stress disrupts TP53 interaction with MDM2. In contrast to MDM2, E3 ubiquitin ligases RNF34 (CARP1) and RFFL (CARP2) can ubiquitinate phosphorylated TP53 (Yang et al. 2007). Binding of MDM2 to TP53 is also inhibited by the tumor suppressor p14-ARF, transcribed from the CDKN2A gene in response to oncogenic signaling or oxidative stress (Zhang et al. 1998, Parisi et al. 2002, Voncken et al. 2005). Ubiquitin-dependant degradation of TP53 can also be promoted by PIRH2 (Leng et al. 2003) and COP1 (Dornan et al. 2004) ubiquitin ligases. HAUSP (USP7) can deubiquitinate TP53, contributing to TP53 stabilization (Li et al. 2002).While post-translational regulation plays a prominent role, TP53 activity is also controlled at the level of promoter function (reviewed in Saldana-Meyer and Recillas-Targa 2011), mRNA stability and translation efficiency (Mahmoudi et al. 2009, Le et al. 2009, Takagi et al. 2005)

external resources
NCBI:1383077
REACTOME:R-HSA-6806003
PUBMED:11883935
PUBMED:11923872
PUBMED:19293287
PUBMED:23303139
PUBMED:17499002
PUBMED:15563468
PUBMED:17121812
PUBMED:21986495
PUBMED:15103385
PUBMED:9529249
PUBMED:21814038
PUBMED:19250907
PUBMED:8319905
PUBMED:7878469
PUBMED:12654245
PUBMED:16213212

genes
AKT1 , AKT2 , ATM , PRDM1 , CCNA2 , CCNG1 , CDK1 , CDK2 , CDKN2A , DAXX , MTOR , MDM2 , MDM4 , PDPK1 , PPP2CA , PPP2CB , PPP2R1A , PPP2R1B , PPP2R5C , RPS27A , SGK1 , TP53 , UBA52 , UBB , UBC , USP7 , CCNA1 , USP2 , AKT3 , CHEK2 , PRR5 , MLST8 , MAPKAP1 , RNF34 , RFFL , RICTOR ,