Okazaki I J, Kim H J, McElvaney N G, Lesma E, Moss J
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1434, USA.
Blood. 1996 Aug 1;88(3):915-21.
Mono ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to proteins. It was reported by Wang et al (J Immunol 153:4048, 1994) that incubation of mouse cytotoxic T lymphocytes (CTL) with NAD resulted in the ADP-ribosylation of membrane proteins and inhibition of cell proliferation and cytotoxicity. Treatment of CTL with phosphatidylinositol-specific phospholipase C (PI-PLC) before incubation with NAD prevented the inhibitory effects of NAD on the cells, consistent with the removal of a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase on the lymphocyte surface. We have identified and cloned a GPI-linked ADP-ribosyltransferase from Yac-1 mouse T-cell lymphoma cells. The deduced amino acid sequence of the Yac-1 transferase was 70% and 41% identical to those of the rabbit skeletal muscle and chicken heterophil, respectively. It contained three noncontiguous sequences similar to those found in several of the bacterial toxin and vertebrate ADP-ribosyltransferases. Based on crystallography of the bacterial toxins, these regions are believed to form, in part, the catalytic site consistent with a common mechanism for the ADP-ribose transfer reaction. In rat mammary adenocarcinoma (NMU) cells transformed with the Yac-1 transferase cDNA, transferase activity was present on the cell surface and was released into the medium by treatment of cells with PI-PLC. Thus, we have cloned a novel gene that has properties identical to the transferase detected in CTL, and may be involved in the NAD-dependent regulation of proliferation and cytotoxicity.
单 ADP-核糖基转移酶催化烟酰胺腺嘌呤二核苷酸（NAD）的 ADP-核糖部分转移至蛋白质上。Wang 等人（《免疫学杂志》153:4048，1994 年）报道，将小鼠细胞毒性 T 淋巴细胞（CTL）与 NAD 一起孵育会导致膜蛋白的 ADP-核糖基化，并抑制细胞增殖和细胞毒性。在用 NAD 孵育之前，先用磷脂酰肌醇特异性磷脂酶 C（PI-PLC）处理 CTL，可防止 NAD 对细胞的抑制作用，这与去除淋巴细胞表面糖基磷脂酰肌醇（GPI）锚定的 ADP-核糖基转移酶一致。我们已从 Yac-1 小鼠 T 细胞淋巴瘤细胞中鉴定并克隆了一种 GPI 连接的 ADP-核糖基转移酶。Yac-1 转移酶推导的氨基酸序列分别与兔骨骼肌和鸡异嗜性细胞的序列有 70%和 41%的同一性。它包含三个不连续的序列，与在几种细菌毒素和脊椎动物 ADP-核糖基转移酶中发现的序列相似。基于细菌毒素的晶体学，这些区域被认为部分形成了与 ADP-核糖转移反应的共同机制一致的催化位点。在用 Yac-1 转移酶 cDNA 转化的大鼠乳腺腺癌（NMU）细胞中，转移酶活性存在于细胞表面，并且通过用 PI-PLC 处理细胞而释放到培养基中。因此，我们克隆了一个新基因，其特性与在 CTL 中检测到的转移酶相同，并且可能参与 NAD 依赖性的增殖和细胞毒性调节。
