Reference - Detail
| RRC ID | 18116 |
|---|---|
| Author | Satow R, Shitashige M, Jigami T, Fukami K, Honda K, Kitabayashi I, Yamada T. |
| Title | β-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells. |
| Journal | Gastroenterology |
| Abstract |
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 β-catenin expression on PML function in these cells. RESULTS:β-catenin specifically interacted with the product of PML transcript variant IV (PML-IV) through the armadillo repeat domain of β-catenin. Overexpression of β-catenin in colorectal cancer cells disrupted the subcellular compartmentalization of PML-IV, whereas knockdown of β-catenin restored formation of PML-NB. Modification of PML by the small ubiquitin-related modifier (SUMO) is required for proper assembly of PML-NB. β-catenin inhibited Ran-binding protein 2-mediated SUMOylation of PML-IV. CONCLUSIONS:β-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 β-catenin. |
| Volume | 142(3) |
| Pages | 572-81 |
| Published | 2012-3-1 |
| DOI | 10.1053/j.gastro.2011.11.041 |
| PII | S0016-5085(11)01639-8 |
| PMID | 22155184 |
| MeSH | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism Cell Nucleus / metabolism Colorectal Neoplasms / genetics Colorectal Neoplasms / metabolism* Colorectal Neoplasms / pathology Gene Expression Regulation, Neoplastic HEK293 Cells HeLa Cells Humans Lysine Molecular Chaperones / metabolism Nuclear Pore Complex Proteins / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Promyelocytic Leukemia Protein Protein Binding Protein Isoforms RNA Interference Small Ubiquitin-Related Modifier Proteins / metabolism Sumoylation Transcription Factor 4 Transcription Factors / genetics Transcription Factors / metabolism* Transcriptional Activation Transfection Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Wnt Signaling Pathway* / genetics beta Catenin / genetics beta Catenin / metabolism* |
| IF | 17.373 |
| Times Cited | 18 |
| WOS Category | GASTROENTEROLOGY & HEPATOLOGY |
| Resource | |
| Human and Animal Cells | HeLa(RCB0007) |