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Structural Studies on the MDM2-MDMX Heterodimer /

  • Author(s): Sano, Eleanor Shoko
  • et al.
Abstract

MDM2 is a protein that regulates p53 to prevent it from performing its tumor suppressor functions. In normal cells, MDM2 acts as an ubiquitin ligase to promote p53 degradation by attaching ubiquitin and sending it to the proteasome. MDMX is another negative p53 regulator that works in tandem with MDM2 by binding via their RING domains for dimerization. Studies have shown that MDM2 and MDMX are over-expressed in certain cancers, and are dependent of one another to function effectively as p53 regulators. Hence, the study of the MDM2-MDMX heterodimer is critical in anti-cancer research to provide more information on how it inactivates p53. By knowing the mechanism of p53 regulation, methods can be produced to inhibit MDM2 and MDMX activities and activate p53 functions for tumor suppression. However, the MDM2-MDMX heterodimer's structure has not been fully elucidated. The main objective of this thesis was the purification of the MDM2-MDMX complex and its subsequent 3D reconstruction using Electron Microscopy

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