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Publication : Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration.

First Author  Balastik M Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  33 Pages  12016-21
PubMed ID  18687884 Mgi Jnum  J:140337
Mgi Id  MGI:3813391 Doi  10.1073/pnas.0802261105
Citation  Balastik M, et al. (2008) Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration. Proc Natl Acad Sci U S A 105(33):12016-21
abstractText  TRIM RING finger proteins have been shown to play an important role in cancerogenesis, in the pathogenesis of some human hereditary disorders, and in the defense against viral infection, but the function of the majority of TRIM proteins remains unknown. Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. Additionally, we show that mice deficient in TRIM2 have increased NF-L level in axons and NF-L-filled axonal swellings in cerebellum, retina, spinal cord, and cerebral cortex. The axonopathy is followed by progressive neurodegeneration accompanied by juvenile-onset tremor and ataxia. Our results demonstrate that TRIM2 is an ubiquitin ligase and point to a mechanism regulating NF-L metabolism through an ubiquitination pathway that, if deregulated, triggers neurodegeneration.
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