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https://doi.org/10.1093/hmg/ddi292
Title: | Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin | Authors: | Sriram S.R. Li X. Ko H.S. Chung K.K.K. Wong E. Lim K.L. Dawson V.L. Dawson T.M. |
Keywords: | Adrenergic Beta Heart failure Lymphocytes Prognosis Receptors Signal transduction |
Issue Date: | 2005 | Publisher: | Oxford University Press | Citation: | Sriram S.R., Li X., Ko H.S., Chung K.K.K., Wong E., Lim K.L., Dawson V.L., Dawson T.M. (2005). Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. Human Molecular Genetics 14 (17) : 2571-2586. ScholarBank@NUS Repository. https://doi.org/10.1093/hmg/ddi292 | Abstract: | Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism. The underlying mechanism of pathogenesis in parkin-associated Parkinson's disease (PD) is thought to be due to the loss of parkin's E3 ubiquitin ligase activity. A subset of missense and nonsense point mutations in parkin that span the entire gene and represent the numerous inheritance patterns that are associated with parkin-linked PD were investigated for their E3 ligase activity, localization and their ability to bind, ubiquitinate and effect the degradation of two substrates, synphilin-1 and aminoacyl-tRNA synthetase complex cofactor, p38. Parkin mutants vary in their intracellular localization, binding to substrates and enzymatic activity, yet they are ultimately deficient in their ability to degrade substrate. These results suggest that not all parkin mutations result in loss of parkin's E3 ligase activity, but they all appear to manifest as loss-of-function mutants due to defects in solubility, aggregation, enzymatic activity or targeting proteins to the proteasome for degradation. � The Author 2005. Published by Oxford University Press. All rights reserved. | Source Title: | Human Molecular Genetics | URI: | http://scholarbank.nus.edu.sg/handle/10635/148919 | ISSN: | 09646906 | DOI: | 10.1093/hmg/ddi292 |
Appears in Collections: | Elements Staff Publications |
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