title: CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein.
abstract: Members of the tumor necrosis factor receptor (TNFR) superfamily are important for cell growth and survival. In addition to providing costimulatory signals for cell proliferation, ligation of both TNFR1 and Fas can result in programmed cell death or apoptosis. The underlying mechanism requires an intact 80-aa stretch present in the cytoplasmic tails of both TNFR1 and Fas, termed the death domain (DD). Here we show that CD27, a member of the TNFR family, expressed on discrete subpopulations 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 apoptosis. Co-crosslinking of surface Ig receptors along with ligation of CD27 augments CD27-mediated apoptosis. Unlike TNFR1 and Fas, the cytoplasmic tail of CD27 is relatively short and lacks the DD. Using the yeast two-hybrid system, we have cloned a novel protein (Siva) that binds 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 Siva in various cell lines induces apoptosis, suggesting an important role for Siva in the CD27-transduced apoptotic pathway.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02120, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Prasad
authors.forename: Z
authors.initials: Z
authors.lastname: Ao
authors.forename: Y
authors.initials: Y
authors.lastname: Yoon
authors.forename: M X
authors.initials: MX
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Rizk
authors.forename: S
authors.initials: S
authors.lastname: Jacquot
authors.forename: S F
authors.initials: SF
authors.lastname: Schlossman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D053938:DNA Fragmentation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C106549:SIVA1 protein, human; C484569:Siva protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7