Functional modulation of parkin through physical interaction with SUMO-1.
Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the extensive and progressive loss of dopaminergic neurons in the CNS substantia nigra pars compacta region. Mutations in the parkin gene, which encodes for E3 ubiquitin ligase, have been implicated in autosomal recessive juvenile parkinsonism, an early-onset and common familial form of PD. Although several parkin substrates have already been identified, the molecular mechanism underlying the regulation of enzymatic activity of parkin has yet to be clarified. In a previous study, we demonstrated that RanBP2 becomes a new target for parkin E3 ubiquitin ligase and is processed via parkin-mediated ubiquitination and subsequent proteasomal degradation. RanBP2, which is localized in the cytoplasmic filament of the nuclear pore complex, belongs to the small ubiquitin-related modifier (SUMO) E3 ligase family. Here we show that parkin appears to bind selectively to the SUMO-1 in vivo and in vitro. Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. Our findings suggest that the E3 ubiquitin ligase activity of parkin and its intracellular localization may be modulated through the SUMO-1 association.
Um
Ji Won
JW
Department of Biology, College of Science, Yonsei University, Seoul, Korea.
Chung
Kwang Chul
KC
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D018832:Molecular Chaperones / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D025842:SUMO-1 Protein / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection / Q000379:methods; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D025842:SUMO-1 Protein; D025801:Ubiquitin; C094493:ran-binding protein 2; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein