[摘要]：BACKGROUND & AIMS: Loss of promyelocytic leukemia protein (PML) nuclear body (NB) formation has been reported in colorectal and other solid tumors. However, genetic alteration of PML is rarely observed in these tumors; the exact mechanisms that mediate loss of PML function are not known. METHODS: We previously used a comprehensive shotgun mass spectrometry approach to identify PML as 1 of 70 proteins that coimmunoprecipitate with anti-T-cell factor 4 in DLD-1 and HCT116 colorectal cancer cell lines; we investigated the effects of altered beta-catenin expression on PML function in these cells. RESULTS: beta-catenin specifically interacted with the product of PML transcript variant IV (PML-IV) through the armadillo repeat domain of beta-catenin. Overexpression of beta-catenin in colorectal cancer cells disrupted the subcellular compartmentalization of PML-IV, whereas knockdown of beta-catenin restored formation of PML-NB. Modification of PML by the small ubiquitin-related modifier (SUMO) is required for proper assembly of PML-NB. beta-catenin inhibited Ran-binding protein 2-mediated SUMOylation of PML-IV. CONCLUSIONS: beta-catenin interacts with PML isoform IV and disrupts PML-IV function and PML-NB formation by inhibiting Ran-binding protein 2-mediated SUMO modification of PML-IV. These findings indicate the involvement of a posttranslational mechanism in disruption of PML-NB organization in cancer cells and provide more information about the oncogenic functions of beta-catenin.
