Regulation Of MDM2 Activity By The Ribosomal Protein L13

The MDM2 protein plays an important role in regulating the stability and function of the p53 tumor suppressor protein. In this report, we show that the ribosomal protein L13 can interact with MDM2 and inhibit MDM2 function, thus leading to the stabilization and activation of p53. Expression of HDM2 alone in cells resulted in localization of HDM2 in the nucleoplasm while L13 expressed alone was found to be localized to the nucleolus. Following coexpression of L13 and MDM2, we were able to detect colocalization of the two proteins in the nucleolus. The inhibition of MDM2's E3 ligase activity by L13 shows some similarity to the previously described activity of L11, and expression of either L11 or L13 can induce a p53 response. Enhancement of the interaction between endogenous L13 and MDM2 following treatment of cells with low levels of actinomycin-D suggests that the MDM2/L13 interaction represents a novel pathway for p53 stabilization in response to perturbations in ribosome biogenesis.The p53 tumor suppressor protein is activated by several cellular stress signals associated with tumor development. Activation of p53 is accompanied by stabilization of the p53 protein following inhibition of MDM2, the ubiquitin ligase for p53. We show here that the ribosomal protein L13 can interact with MDM2 and inhibit the degradation of p53, and provide evidence that the MDM2/L13 interaction is enhanced in response to perturbations in ribosome biogenesis. Our results therefore identify a novel pathway for p53 induction under these conditions and provide a target for the design of drugs to reactivate p53.Full-length USP2a associates with Mdm2 in cells where it can deubiquitinate Mdm2. Ectopic expression of USP2a causes accumulation of Mdm2 in a dose-dependent manner and consequently promotes Mdm2-mediated p53 degradation. In this study we show that RPL13 inhibits USP2a's function of deubiquitinating MDM2. Meanwhile, the protein of UCHL2 has a similar function to USP2a, and the relationship between USP2a and UCHL2 hasn't been proved.