Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/101043
Title: Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy
Authors: Tan, J.M.M.
Wong, E.S.P.
Dawson, V.L.
Dawson, T.M.
Lim, K.-L. 
Keywords: Autophagy
Neurodegeneration
p62
Proteasome
Protein aggregates
Ubc13
Ubiquitin
Issue Date: 16-Feb-2008
Citation: Tan, J.M.M., Wong, E.S.P., Dawson, V.L., Dawson, T.M., Lim, K.-L. (2008-02-16). Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy. Autophagy 4 (2) : 251-253. ScholarBank@NUS Repository.
Abstract: Although protein inclusions associated with neurodegenerative diseases are typically enriched with ubiquitin, it is currently unclear whether the topology of ubiquitin linkage plays a role in their biogenesis. In an attempt to clarify this, our recent work identified K63-linked polyubiquitin as a key regulator of inclusion dynamics. We found in the setting of ectopic overexpression of different ubiquitin species in cultured cells that K63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions linked to several major neurodegenerative diseases. Further supporting this, we report here a similar phenomenon in cells co-expressing Ubc13 and Uev1a but not those expressing UbcH7 or UbcH8. Notably, Ubc13 in association with Uev1a is known to promote K63-linked ubiquitination. In exploring how K63-linked ubiquitination could promote the clearance of inclusions by autophagy, we also found in our current study that K63-linked polyubiquitin interacts with p62, a ubiquitin-binding protein previously demonstrated by others to facilitate autophagy-mediated clearance of inclusions. Further, K63 ubiquitin-positive inclusions were found to be enriched with p62. Given the observed intimate relationship between p62 and K63 polyubiquitin, our results suggest that p62 and K63-linked polyubiquitin may function as key partners involved in directing clearance of protein inclusions by autophagy. ©2008 Landes Bioscience.
Source Title: Autophagy
URI: http://scholarbank.nus.edu.sg/handle/10635/101043
ISSN: 15548627
Appears in Collections:Staff Publications

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