Identification of far upstream element-binding protein-1 as an authentic Parkin substrate.

Abstract	Aminoacyl-tRNA synthetase-interacting multifunctional protein type 2 was recently identified as an authentic substrate of the ubiquitin E3 ligase, parkin, a gene associated with autosomal recessive juvenile parkinsonism. Far upstream element-binding protein 1 is known to be degraded in an aminoacyl-tRNA synthetase interacting multifunctional protein type 2 dependent manner, which is crucial for lung cell maturation in early development. Therefore, we wondered whether far upstream element-binding protein 1 levels are altered in the absence of Parkin and in Parkinson disease. We herein report that far upstream element-binding protein 1 accumulates in Parkin knock-out mice, patients with autosomal recessive juvenile parkinsonism, sporadic Parkinson disease, and diffuse Lewy Body disease as well as the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. Moreover, Parkin interacts with and ubiquitinates far upstream element-binding protein 1 facilitating its degradation through the ubiquitin proteasome system. Taken together, these results suggest that far upstream element-binding protein 1 is an authentic substrate of Parkin and that far upstream element-binding protein 1 might play an important role in development of Parkinson disease pathology along with aminoacyl-tRNA synthetase interacting multifunctional protein type 2.
Authors	Han Seok Ko, Seong Who Kim, Sathya R Sriram, Valina L Dawson, Ted M Dawson
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 24 Pg. 16193-6 (Jun 16 2006) ISSN: 0021-9258 [Print] United States
PMID	16672220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins FUBP1 protein, human Fubp protein, mouse RNA-Binding Proteins Ubiquitin-Protein Ligases parkin protein DNA Helicases Amino Acyl-tRNA Synthetases
Topics	Amino Acyl-tRNA Synthetases (metabolism) Animals Brain (metabolism) DNA Helicases (chemistry, metabolism) DNA-Binding Proteins (chemistry, metabolism) Gene Expression Regulation Humans Mice Mice, Knockout Mice, Transgenic Protein Binding RNA-Binding Proteins Tissue Distribution Ubiquitin-Protein Ligases (chemistry, metabolism)

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