Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival

• DOI: 10.1186/s12943-015-0334-0
• Publication Date: 2015-03-25T10:01:41Z
• Authors: Tao Liu; Hailong Zhang; Jing Xiong; Sha Yi; Lubing Gu; Muxiang Zhou
• Keywords: XIAP; Immunoprecipitation

It is known that the MDM2 protein stabilized when it forms a heterodimer with its partner MDM4, but stability in homodimer form not known. The contains C-terminal RING domain only functions as an E3 ligase to regulate ubiquitination of p53 and itself, also characterized be able bind several specific cellular mRNAs gene expression. In this study, we evaluate whether regulated by binding small RNA (XIAP IRES mRNA).We performed chemical cross-linking bimolecular fluorescence complementation (BiFC) assay measure human effect XIAP on homodimerization stabilization. Ubiquitination pulse-chase assays were used detect self-ubiquitination turn-over. Fluorescent titration ITC examine between IRES. Western blot was for determining Clonogenic assay, WST flow cytometry test effects IRES, siXIAP IR cancer cell growth apoptosis.We found self-association (homodimerization) occurs through becomes unstable homodimerized. resulted increased function self-ubiquitination. Binding inhibited self-ubiquitination, which stabilization MDM2, well Upregulation led inhibition survival both p53-normal -deficient cells.Our study identified new interacts regulates stabilization, suggested targeting disruption protein-RNA interaction might useful strategy developing novel anti-cancer therapeutics.