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The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-κB target genes by interaction with NFKBIZ

Oncogene volume 28, pages 270–278 (2009)Cite this article

Abstract

FUS (also called TLS), EWSR1 and TAF15 (also called TAF2N) are related genes involved in tumor type-specific fusion oncogenes in human malignancies. The FUS-DDIT3 fusion oncogene results from a t(12;16)(q13;p11) chromosome translocation and has a causative role in the initiation of myxoid/round cell liposarcomas (MLS/RCLS). The FUS-DDIT3 protein induces increased expression of the CAAT/enhancer-binding protein (C/EBP) and nuclear factor-κB (NF-κB)-controlled gene IL8, and the N-terminal FUS part is required for this activation. Chromatin immunoprecipitation analysis showed that FUS-DDIT3 binds the IL8 promoter. Expression studies of the IL8 promoter harboring a C/EBP–NF-κB composite site pinpointed the importance of NF-κB for IL8 expression in FUS-DDIT3-expressing cells. We therefore probed for possible interaction of FUS-DDIT3 with members of the NF-κB family. The nuclear factor NFKBIZ colocalizes with FUS-DDIT3 in nuclear structures, and immunoprecipitation experiments showed that FUS-DDIT3 binds the C-terminal of NFKBIZ. We also report that additional NF-κB-controlled genes are upregulated at the mRNA level in FUS-DDIT3-expressing cell lines and they can be induced by NFKBIZ. Taken together, the results indicate that FUS-DDIT3 deregulates some NF-κB-controlled genes through interactions with NFKBIZ. Similar mechanisms may be a part of the transformation process in other tumor types carrying FUS, EWSR1 and TAF15 containing fusion oncogenes.

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Acknowledgements

We thank Ulric Pedersen for image processing. This work was supported by grants from the Inga-Britt and Arne Lundberg Research Foundation, the Swedish Cancer Society, Assar Gabrielssons Research Foundation and the Johan Jansson Foundation for Cancer Research. RM was supported by an AIRC grant. AS is supported by a postdoctoral fellowship award from the Swedish Research Council.

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  1. Department of Pathology, Lundberg Laboratory for Cancer Research (LLCR), Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    M Göransson, M K Andersson, C Andersson, A Olofsson & P Åman

  2. Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milano, Italy

    C Forni & R Mantovani

  3. Department of Clinical Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation (CBR), Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    A Ståhlberg

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Correspondence to P Åman.

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Göransson, M., Andersson, M., Forni, C. et al. The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-κB target genes by interaction with NFKBIZ. Oncogene 28, 270–278 (2009). https://doi.org/10.1038/onc.2008.378

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