Saito T, Ishiguro K, Onuki R, Nagai Y, Kishimoto T, Hisanaga S
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-ohsawa, Tokyo, Hachiohji, 192-0397, Japan.
Biochem Biophys Res Commun. 1998 Nov 27;252(3):775-8. doi: 10.1006/bbrc.1998.9739.
Degradation of p35, a neuron-specific activator of CDK5, was studied in rat cortical neurons in primary culture. Treatment of cultured neurons with cyclohexamide induced the rapid disappearance of p35 accompanied by parallel inactivation of the kinase activity of CDK5. The disappearance of p35 was blocked with proteasome inhibitors benzyloxycarbonyl-leucyl-leucyl-leucinal and lactacystin, indicating the involvement of proteasome. The degradation of p35 was induced with okadaic acid in the presence of ATP in neuron extracts. The degradation of p35 by proteasome in cultured neurons was stimulated by okadaic acid in the absence of cyclohexamide. These results indicate that p35 is degraded by proteasome in a phosphorylation-dependent manner in neurons.
在原代培养的大鼠皮层神经元中研究了细胞周期蛋白依赖性激酶5（CDK5）的神经元特异性激活剂p35的降解情况。用环己酰亚胺处理培养的神经元会导致p35迅速消失，同时伴随着CDK5激酶活性的平行失活。蛋白酶体抑制剂苄氧羰基 - 亮氨酰 - 亮氨酰 - 亮氨酸醛和乳胞素可阻断p35的消失，表明蛋白酶体参与其中。在神经元提取物中，冈田酸在ATP存在的情况下可诱导p35的降解。在没有环己酰亚胺的情况下，冈田酸可刺激培养神经元中蛋白酶体对p35的降解。这些结果表明，在神经元中，p35以磷酸化依赖的方式被蛋白酶体降解。
