Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice
Article first published online: 27 SEP 2005
Journal of Neurochemistry
Volume 95, Issue 3, pages 724–731, November 2005
How to Cite
Anderson, C., Crimmins, S., Wilson, J. A., Korbel, G. A., Ploegh, H. L. and Wilson, S. M. (2005), Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice. Journal of Neurochemistry, 95: 724–731. doi: 10.1111/j.1471-4159.2005.03409.x
- Issue published online: 27 SEP 2005
- Article first published online: 27 SEP 2005
- Received May 20, 2005; revised manuscript received June 24, 2005; accepted June 30, 2005.
- ubiquitin-specific protease 14
The ataxia (axJ) mutation is a spontaneous recessive mutation that results in reduced expression of ubiquitin-specific protease 14, Usp14. Mice homozygous for the axJ 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 axJ mice. Usp14 co-fractionated with proteasomes isolated from livers and brains of wild-type mice. Proteasomes isolated from the axJ 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 axJ 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.