The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-[kappa]B target genes by interaction with NFKBIZ.
Goransson, M 1; Andersson, M K 1; Forni, C 2; Stahlberg, A 3; Andersson, C 1; Olofsson, A 1; Mantovani, R 2; Aman, P 1
[Article] Oncogene. 28(2):270-278, January 15, 2009.

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: 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-[kappa]B (NF-[kappa]B)-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-[kappa]B composite site pinpointed the importance of NF-[kappa]B for IL8 expression in FUS-DDIT3-expressing cells. We therefore probed for possible interaction of FUS-DDIT3 with members of the NF-[kappa]B 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-[kappa]B-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-[kappa]B-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.

Oncogene (2009) 28, 270-278; doi:10.1038/onc.2008.378; published online 13 October 2008

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