Identification of Far Upstream Element-binding Protein-1 as an Authentic Parkin Substrate

• Published in: The Journal of biological chemistry Vol. 281; no. 24; pp. 16193 - 16196
• Main Authors: Ko, Han Seok, Kim, Seong Who, Sriram, Sathya R., Dawson, Valina L., Dawson, Ted M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-06-2006; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acyl-tRNA Synthetases - metabolism; Animals; Brain - metabolism; DNA Helicases - chemistry; DNA Helicases - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Humans; Mice; Mice, Knockout; Mice, Transgenic; Protein Binding; RNA-Binding Proteins; Tissue Distribution; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C600041200

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.