Predicted functions of MdmX in fine-tuning the response of p53 to DNA damage.

ABSTRACT: Tumor suppressor protein p53 is regulated by two structurally homologous proteins, Mdm2 and MdmX. In contrast to Mdm2, MdmX lacks ubiquitin ligase activity. Although the essential interactions of MdmX are known, it is not clear how they function to regulate p53. The regulation of tumor suppressor p53 by Mdm2 and MdmX in response to DNA damage was investigated by mathematical modeling of a simplified network. The simplified network model was derived from a detailed molecular interaction map (MIM) that exhibited four coherent DNA damage response pathways. The results suggest that MdmX may amplify or stabilize DNA damage-induced p53 responses via non-enzymatic interactions. Transient effects of MdmX are mediated by reservoirs of p53ratioMdmX and Mdm2ratioMdmX heterodimers, with MdmX buffering

SUBMITTER: Kim S 

PROVIDER: S-EPMC2824598 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature