Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice
Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice
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DOI：
10.1111/j.1471-4159.2005.03409.x
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
Wilson, SM
中科院分区：
文献类型：
--
作者：
Anderson, C;Crimmins, S;Wilson, SM
共济失调（ax（J））突变是一种自发的隐性突变，导致泛素特异性蛋白酶14（Usp 14）表达减少。ax（J）突变纯合子小鼠生长迟缓，并表现出几种行为障碍，包括静止性震颤和后肢瘫痪。虽然病理缺陷似乎仅限于中枢神经系统，但ax（J）小鼠中Usp 14表达的减少是普遍的。与从野生型小鼠的肝和脑中分离的蛋白酶体共分级分离的Usp 14。从ax（J）脑中分离的蛋白酶体仍然具有去泛素化活性，并在体外具有水解20S蛋白酶体底物的功能。然而，在检查的大多数ax（J）组织中，单体泛素的水平降低了约35%。这些结果表明，Usp14的功能，以维持细胞水平的单体泛素在哺乳动物细胞中，并在泛素水平的改变可能有助于神经系统疾病。
The ataxia (ax(J)) mutation is a spontaneous recessive mutation that results in reduced expression of ubiquitin-specific protease 14, Usp14. Mice homozygous for the ax(J) mutation are retarded for growth and exhibit several behavioral disorders, including a resting tremor and hindlimb paralysis. Although pathological defects appear to be limited to the central nervous system, reduction of Usp14 expression was widespread in the ax(J) mice. Usp14 co-fractionated with proteasomes isolated from livers and brains of wildtype mice. Proteasomes isolated from the ax(J) brains still possessed deubiquitinating activity and were functionally competent to hydrolyze 20S proteasomal substrates in vitro. However, the levels of monomeric ubiquitin were reduced approximately 35% in most of the ax(J) tissues examined. These results indicate that Usp14 functions to maintain the cellular levels of monomeric ubiquitin in mammalian cells, and that alterations in the levels of ubiquitin may contribute to neurological disease.