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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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DRIVES NEUROBLASTOMA TUMORIGENESIS THROUGH EFFECTS ON USP3 AND MYCN STABILITY Article Open access 25 March 2021 REFERENCES * Åman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M,

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TLS: nucleolar localization when transcription is inhibited. _Oncogene_ 14: 451–461. Article  CAS  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS

AND AFFILIATIONS * 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 * Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milano, Italy C Forni & R Mantovani * Department of Clinical

Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation (CBR), Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden A Ståhlberg Authors * M Göransson View

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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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Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * MLS/RCLS * FUS * DDIT3 * NF-κB * NFKBIZ * sarcoma