CD27, A MEMBER OF THE TUMOR-NECROSIS-FACTOR RECEPTOR FAMILY, INDUCES APOPTOSIS AND BINDS TO SIVA, A PROAPOPTOTIC PROTEIN

Members of the tumor necrosis factor receptor (TNFR) superfamily are i mportant for cell growth and survival, In addition to providing costim ulatory signals for cell proliferation, ligation of both TNFR1 and Fas can result in programmed cell death or apoptosis, The underlying mech anism requires an intact 80-aa stretch present in the cytoplasmic tail s of both TNFR1 and Fas, termed the death domain (DD). Here we show th at CD27, a member of the TNFR family expressed on discrete subpopulati ons of T and B cells and known to provide costimulatory signals for T and B cell proliferation and B cell Ig production, can also induce apo ptosis. Co-crosslinking of surface Ig receptors along with ligation of CD27 augments CD27-mediated apoptosis. Unlike TNFR1 and Fas, the cyto plasmic tail of CD27 is relatively short and lacks the DD. Using the y east two-hybrid system, we have cloned a novel protein (Siva) that hin ds to the CD27 cytoplasmic tail, It has a DD homology region, a box-B- like ring finger, and a zinc finger-like domain, Overexpression of Siv a in various cell lines induces apoptosis, suggesting an important rol e for Siva in the CD27-transduced apoptotic pathway.