PEG3 PW1 IS AN IMPRINTED GENE INVOLVED IN THE TNF-NF-KAPPA-B SIGNAL-TRANSDUCTION PATHWAY/

Tumor necrosis factor (TNF) mediates a variety of biological activitie s including cell proliferation, differentiation and programmed cell de ath. The specific response to TNF depends upon cell type and reflects the presence of specific regulatory proteins that participate in the T NF response pathway. TNF signal transduction is mediated by TRAF2 whic h binds the TNF Receptor2 (TNFR2) and activates NF kappa B. We previou sly identified a gene Pw1, which encodes a large zinc-finger containin g protein(1). We have determined that Pw1 is identical to Peg3, a pate rnally expressed gene of unknown function(2) (and will therefore be re ferred to as Peg3 throughout this text). We report here that Peg3 asso ciates specifically with TRAF2 but not with other TRAF family members. Peg3 expression activates NF kappa B via I kappa B-NF kappa B dissoci ation and acts synergistically with TRAF2. Transfection of a truncated Peg3 containing the TRAF2 interaction site, abolishes NF kappa B acti vation by TRAF2 and/or TNF. We conclude that Peg3 is a regulator of th e TNF response. These data reveal the involvement of an imprinted gene in this pathway.