Sign up for Table of Contents Alerts!

Email this page

Print this page

Article Addendum

Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy

Jeanne M.M Tan, Esther S.P. Wong, Valina L. Dawson, Ted Dawson and Kah-Leong Lim

Purchase article for $19

Subscribe to this journal for $99/year

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.

Addendum to: Tan JMM, Wong ESP, Kirkpatrick DS, Pletnikova O, Ko HS, Tay S-P, Ho M.W.L., Troncoso J, Gygi SP, Lee MK, Dawson VL, Dawson TM, Lim K-L. Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases. Human Mol Genet; In press.

Authors

Jeanne M.M Tan

National Neuroscience Institute

Esther S.P. Wong

National Neuroscience Institute

Valina L. Dawson

Johns Hopkins University School of Medicine

Ted Dawson

Johns Hopkins University School of Medicine

Kah-Leong Lim

National Neuroscience Institute

Purchase article for $19

Subscribe to this journal for $99/year