Involvement of the pro-oncoprotein TLS (translocated in liposarcoma) in nuclear factor-kappa B p65-mediated transcription as a coactivator

In this study, we have demonstrated that translocated in liposarcoma (TLS), also termed FUS, is an interacting molecule of the p65 (Re1A) subunit of t he transcription factor nuclear factor kappaB (NF-kappaB) using a yeast two -hybrid screen. We confirmed the interaction between TLS and p65 by the pul l-down assay in vitro and by a coimmunoprecipitation experiment followed by Western blot of the cultured cell in vivo, TLS was originally identified a s part of a fusion protein with CHOP arising from chromosomal translocation in human myxoid liposarcomas. TLS has been shown to be involved in TFIID c omplex formation and associated with RNA polymerase II. However, the role o f TLS in transcriptional regulation has not yet been clearly elucidated. We found that TLS en hanced the NF-kappaB-mediated transactivation induced by physiological stimuli such as tumor necrosis factor alpha, interleukin-1 b eta, and overexpression of NF-kappaB-inducing kinase, TLS augmented NF-kapp aB-dependent promoter activity of the intercellular adhesion molecule-1 gen e and interferon-beta gene. These results suggest that TLS acts as a coacti vator of NF-kappaB and plays a pivotal role in the NP-kappaB-mediated trans activation.