Coffman F D, Fresa K L, Oglesby I, Cohen S
Department of Pathology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Cell Immunol. 1991 Dec;138(2):381-9. doi: 10.1016/0008-8749(91)90162-5.
Proliferating lymphocytes contain an intracellular factor, ADR (activator of DNA replication), which can initiate DNA synthesis in isolated quiescent nuclei. Resting lymphocytes lack ADR activity and contain an intracellular inhibitory factor that suppresses DNA synthesis in normal but not transformed nuclei. In this study we describe a MOLT-4 subline that produces both the activator and inhibitory activities which can be separated by ammonium sulfate fractionation. The inhibitor is heat stable and inhibits ADR-mediated DNA replication in a dose-dependent manner. It does not inhibit DNA polymerase alpha activity. The inhibitor must be present at the initiation of DNA replication to be effective, as it loses most of its effectiveness if it is added after replication has begun. The presence of inhibitory activity in proliferating MOLT-4 cells, taken with the previous observation that inhibitor derived from normal resting cells does not affect DNA synthesis by MOLT-4 nuclei, suggests that failure of a down-regulating signal may play an important role in proliferative disorder.
增殖淋巴细胞含有一种细胞内因子，即ADR（DNA复制激活剂），它能在分离的静止细胞核中启动DNA合成。静止淋巴细胞缺乏ADR活性，并含有一种细胞内抑制因子，该抑制因子可抑制正常细胞核而非转化细胞核中的DNA合成。在本研究中，我们描述了一个MOLT - 4亚系，它能产生激活活性和抑制活性，这两种活性可通过硫酸铵分级分离。该抑制剂热稳定，以剂量依赖方式抑制ADR介导的DNA复制。它不抑制DNA聚合酶α活性。抑制剂必须在DNA复制开始时存在才有效，因为如果在复制开始后添加，它会失去大部分效力。增殖的MOLT - 4细胞中存在抑制活性，结合之前的观察结果，即来自正常静止细胞的抑制剂不影响MOLT - 4细胞核的DNA合成，这表明下调信号的缺失可能在增殖性疾病中起重要作用。
