Walleye dermal sarcoma virus rv-cyclin inhibits NF-κB-dependent transcription

The retroviral cyclin protein (rv-cyclin) of walleye dermal sarcoma virus contains two known functional domains, a cyclin box motif and a carboxy terminal transcription activation domain (AD). The AD contacts TATA-binding protein-associated factor 9 (TAF9), and this action is necessary for both positive and negative regulation of transcription from host and viral promoters. Negative regulation occurs via interference with TAF9 binding by transcriptional activators. Transcription factors that share a functional TAF9-binding motif include NF-κB. Rv-cyclin down regulates NF-κB-dependent transcription, whether induced by TNFα or by direct phosphorylation of IκB by expressed MEKK1. In rv-cyclin-expressing cells, NF-κB p65 is phosphorylated and translocated to the nucleus, where it forms heterodimers with p50 and binds NF-κB response elements. Furthermore, interference with NF-κB is dependent upon an intact TAF9-binding motif in rv-cyclin. The outcome of this NF-κB down regulation is likely to be important in the control of virus replication and tumorigenesis.