An B, Dou Q P
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Cancer Res. 1996 Feb 1;56(3):438-42.
We had found that in an early stage of DNA damage-induced, p53-independent apoptosis, retinoblastoma (RB) protein is hypophosphorylated to a p115 form by an activated serine/threonine phosphatase. Here, we report that accompanying the internucleosomal fragmentation of DNA, the newly formed p115/hypo/RB was immediately cleaved into at least two fragments, p68 and p48. The RB cleavage activity possessed properties of interleukin 1 beta-converting enzyme family. Addition of a specific tetrapeptide interleukin 1 beta-converting enzyme inhibitor prevented cleavage of p115/hypo/RB and early apoptotic cells from undergoing further apoptosis. We suggest that activation of the RB phosphatase and protease may be involved in mediating the two physiological stages of apoptosis, commitment and execution, respectively.
我们发现，在DNA损伤诱导的早期、p53非依赖性凋亡过程中，视网膜母细胞瘤（RB）蛋白被一种活化的丝氨酸/苏氨酸磷酸酶低磷酸化形成p115形式。在此，我们报告，伴随DNA的核小体间断裂，新形成的p115/低磷酸化/RB立即被切割成至少两个片段，p68和p48。RB切割活性具有白细胞介素1β转化酶家族的特性。添加特异性四肽白细胞介素1β转化酶抑制剂可阻止p115/低磷酸化/RB的切割以及早期凋亡细胞进一步凋亡。我们认为，RB磷酸酶和蛋白酶的激活可能分别参与介导凋亡的两个生理阶段，即启动和执行。
