The FUS-DDIT3 Interactome in Myxoid Liposarcoma.
| Autor: | Yu JSE; Department of Pathology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Electronic address: jamiesyu@mail.ubc.ca., Colborne S; British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada. Electronic address: seccolborne@gmail.com., Hughes CS; British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada. Electronic address: chughes@bcgsc.ca., Morin GB; British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada. Electronic address: gmorin@bcgsc.ca., Nielsen TO; Department of Pathology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Electronic address: torsten@mail.ubc.ca. |
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| Jazyk: | angličtina |
| Zdroj: | Neoplasia (New York, N.Y.) [Neoplasia] 2019 Aug; Vol. 21 (8), pp. 740-751. Date of Electronic Publication: 2019 Jun 17. |
| DOI: | 10.1016/j.neo.2019.05.004 |
| Abstrakt: | Myxoid liposarcoma is a malignant lipogenic tumor that develops in deep soft tissues. While local control rates are good, current chemotherapy options remain ineffective against metastatic disease. Myxoid liposarcoma is characterized by the FUS-DDIT3 fusion oncoprotein that is proposed to function as an aberrant transcription factor, but its exact mechanism of action has remained unclear. To identify the key functional interacting partners of FUS-DDIT3, this study utilized immunoprecipitation-mass spectrometry (IP-MS) to identify the FUS-DDIT3 interactome in whole cell lysates of myxoid liposarcoma cells, and results showed an enrichment of RNA processing proteins. Further quantitative MS analyses of FUS-DDIT3 complexes isolated from nuclear lysates showed that members of several chromatin regulatory complexes were present in the FUS-DDIT3 interactome, including NuRD, SWI/SNF, PRC1, PRC2, and MLL1 COMPASS-like complexes. Co-immunoprecipitation validated the associations of FUS-DDIT3 with BRG1/SMARCA4, BAF155/SMARCC1, BAF57/SMARCE1, and KDM1A. Data from this study provides candidates for functional validation as potential therapeutic targets, particularly for emerging epigenetic drugs. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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