Regulation of p53 family members by the ubiquitin-like SUMO system

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

“…29 Interestingly, reports indicate that interaction of Ubc9 and p53 may be regulated by p53 phosphorylation. 30 In addition, MDM2 can promote sumoylation of p53 in cooperation with p14 ARF , a protein that binds MDM2 and inhibits ubiquitination.…”

“…35,36 Functionally, it has been proposed that sumoylation of p53 may regulate protein-protein interactions, half-life and/or subcellular localization. 29,37 Now, we report that RAX/PACT, the only identified cellular activator of PKR, can form a complex with p53 and the sumo-conjugating enzyme Ubc9 to induce p53 sumoylation at lysine 386. This promotes sumoylation-dependent transcriptional activation of p53, leading to G 1 cell cycle arrest.…”

The Ubiquitin-Proteasome System and DNA Repair

“…Additionally, both p53 and Mdm2 are modified by SUMO-1 . Only a small fraction of p53 is sumoylated, and the possible role of p53 sumoylation in degradation and DNA repair is still being investigated (Stehmeier & Muller, 2009). Similarly, proliferating cell nuclear antigen (PCNA), a processivity clamp for the replicative and repair DNA polymerases, is a target of the UPS (Paunesku et al, 2001;Ulrich, 2009).…”

“…In both cases, their UPS regulation can be either proteolytic or non-proteolytic (Coutts et al, 2009;Ulrich, 2009). p53 is regulated by the UPS in a way that prevents unnecessary cell death or cell-cycle arrest (Stehmeier & Muller, 2009). p53 interacts with the 19S proteasome in vitro and in vivo (Zhu et al, 2007) and can be both mono-or polyubiquitinated (Stehmeier & Muller, 2009).…”

“…p53 is regulated by the UPS in a way that prevents unnecessary cell death or cell-cycle arrest (Stehmeier & Muller, 2009). p53 interacts with the 19S proteasome in vitro and in vivo (Zhu et al, 2007) and can be both mono-or polyubiquitinated (Stehmeier & Muller, 2009). Mdm2, a ubiquitin-protein ligase, promotes the ubiquitination and consequent degradation of p53 as well as the conjugation of NEDD8 (Zhang & Xiong, 2001;Xirodimas et al, 2004).…”