Misfolding, not ubiquitylation, underlies protein targeting to inclusion bodies
Abstract/Contents
- Abstract
- Inclusion bodies (IB) containing aggregated forms of disease-associated proteins and polyubiquitin conjugates are universal histopathological features of neurodegenerative disease, but the mechanisms that govern recruitment of ubiquitinated proteins to IB are not well understood. Ubiquitin (Ub) has previously been proposed to target proteins to IB for degradation. In this study, we use conditionally destabilized reporters that undergo misfolding and ubiquitination upon removal of stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IB composed of an N-terminal fragment of mutant huntingtin (htt), the causative protein in Huntington's disease (HD). We show that reporters are excluded from IB in the presence of stabilizing ligand, but are recruited to IB following ligand washout. However, we find that Ub conjugation is not necessary or sufficient to target reporters to IB. Moreover, misfolded reporters and Ub conjugates are stable at IB. These data indicate that compromised folding states, not conjugation to Ub, specifies IB recruitment.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bersuker, Kirill |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Kopito, Ron Rieger |
| Thesis advisor | Kopito, Ron Rieger |
| Thesis advisor | Skotheim, Jan, 1977- |
| Thesis advisor | Wandless, Thomas |
| Advisor | Skotheim, Jan, 1977- |
| Advisor | Wandless, Thomas |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Kirill Bersuker. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Kirill Bersuker
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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