Tian Q, Streuli M, Saito H, Schlossman S F, Anderson P
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Cell. 1991 Nov 1;67(3):629-39. doi: 10.1016/0092-8674(91)90536-8.
Cytolytic lymphocytes (CTLs) are characterized by their inclusion of cytoplasmic granules containing effector molecules such as perforin and the serine proteases. Here we describe the cDNA cloning and functional characterization of two related isoforms of a cytolytic granule protein designated TIA-1. Sequence analysis reveals that the 40 kd TIA-1 isoform (rp40-TIA-1) is structurally related to the poly(A)-binding proteins, possessing three RNA-binding domains and a carboxy-terminal, glutamine-rich auxiliary domain. The 15 kd TIA-1 isoform, the major species present in cytolytic granules, appears to be derived from the carboxy-terminal auxiliary domain of rp40-TIA-1 by proteolytic processing. Both natural and recombinant TIA-1 were found to induce DNA fragmentation in digitonin permeabilized thymocytes, suggesting that these molecules may be the granule components responsible for inducing apoptosis in CTL targets.
细胞溶解性淋巴细胞（CTLs）的特征在于其包含含有诸如穿孔素和丝氨酸蛋白酶等效应分子的细胞质颗粒。在此，我们描述了一种称为TIA-1的细胞溶解性颗粒蛋白的两种相关同工型的cDNA克隆及功能特性。序列分析显示，40kd的TIA-1同工型（rp40-TIA-1）在结构上与聚（A）结合蛋白相关，具有三个RNA结合结构域和一个富含谷氨酰胺的羧基末端辅助结构域。15kd的TIA-1同工型是细胞溶解性颗粒中的主要种类，似乎是通过蛋白水解加工从rp40-TIA-1的羧基末端辅助结构域衍生而来。天然和重组的TIA-1均被发现可在洋地黄皂苷通透化的胸腺细胞中诱导DNA片段化，这表明这些分子可能是负责在CTL靶标中诱导细胞凋亡的颗粒成分。
