Ageta H, Kato A, Hatakeyama S, Nakayama K, Isojima Y, Sugiyama H
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
J Biol Chem. 2001 May 11;276(19):15893-7. doi: 10.1074/jbc.M011097200. Epub 2001 Feb 21.
The vesl-1S/homer-1a gene is up-regulated during seizure and long term potentiation. Other members of the Vesl family, Vesl-1L, -2, and -3, are constitutively expressed in the brain. We examined the regulatory mechanisms governing the expression level of Vesl-1S protein, either an exogenously introduced one in COS7 or human embryonic kidney 293T cells or an endogenous one in rat brain neurons in cultures. In both cases, application of proteasome inhibitors increased the amount of Vesl-1S protein but not that of Vesl-1L, -2, or -3 protein. Deletion analyses revealed that the C-terminal 11-amino acid region was responsible for the proteolysis of Vesl-1S by proteasomes. Application of proteasome inhibitors promoted ubiquitination of Vesl-1S protein but not that of the Vesl-1S deletion mutant, which evaded proteasome-mediated degradation. These results indicate that ubiquitin-proteasome systems are involved in the regulation of the expression level of Vesl-1S protein.
Vesl-1S/homer-1a基因在癫痫发作和长期增强过程中上调。Vesl家族的其他成员，Vesl-1L、-2和-3，在大脑中组成性表达。我们研究了在COS7或人胚肾293T细胞中外源导入的Vesl-1S蛋白或培养的大鼠脑神经元中内源性Vesl-1S蛋白表达水平的调控机制。在这两种情况下，蛋白酶体抑制剂的应用增加了Vesl-1S蛋白的量，但没有增加Vesl-1L、-2或-3蛋白的量。缺失分析表明，C末端的11个氨基酸区域负责蛋白酶体对Vesl-1S的蛋白水解。蛋白酶体抑制剂的应用促进了Vesl-1S蛋白的泛素化，但没有促进逃避蛋白酶体介导降解的Vesl-1S缺失突变体的泛素化。这些结果表明，泛素-蛋白酶体系统参与了Vesl-1S蛋白表达水平的调控。
