Prasad K V, Ao Z, Yoon Y, Wu M X, Rizk M, Jacquot S, Schlossman S F
Division of Tumor Immunology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02120, USA.
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6346-51. doi: 10.1073/pnas.94.12.6346.
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.
肿瘤坏死因子受体（TNFR）超家族成员对细胞生长和存活至关重要。除了为细胞增殖提供共刺激信号外，TNFR1和Fas的连接均可导致程序性细胞死亡或凋亡。其潜在机制需要TNFR1和Fas细胞质尾部存在一个完整的80个氨基酸的片段，称为死亡结构域（DD）。在此我们表明，CD27是TNFR家族的成员，在T细胞和B细胞的离散亚群上表达，已知可为T细胞和B细胞增殖以及B细胞Ig产生提供共刺激信号，它也能诱导凋亡。表面Ig受体的共交联以及CD27的连接可增强CD27介导的凋亡。与TNFR1和Fas不同，CD27的细胞质尾部相对较短且缺乏DD。利用酵母双杂交系统，我们克隆了一种与CD27细胞质尾部结合的新型蛋白质（Siva）。它具有一个DD同源区域、一个类似Box-B的环指结构和一个类似锌指的结构域。Siva在各种细胞系中的过表达诱导凋亡，提示Siva在CD27转导的凋亡途径中起重要作用。
