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@ARTICLE{Aron:141978,
author = {R. Aron and P. Pellegrini and E. Green$^*$ and D. C.
Maddison and K. Opoku-Nsiah and J. S. Wong and A. C. Daub
and F. Giorgini and S. Finkbeiner},
title = {{D}eubiquitinase {U}sp12 functions noncatalytically to
induce autophagy and confer neuroprotection in models of
{H}untington's disease.},
journal = {Nature Communications},
volume = {9},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2018-02208},
pages = {3191},
year = {2018},
abstract = {Huntington's disease is a progressive neurodegenerative
disorder caused by polyglutamine-expanded mutant huntingtin
(mHTT). Here, we show that the deubiquitinase Usp12 rescues
mHTT-mediated neurodegeneration in Huntington's disease
rodent and patient-derived human neurons, and in Drosophila.
The neuroprotective role of Usp12 may be specific amongst
related deubiquitinases, as the closely related homolog
Usp46 does not suppress mHTT-mediated toxicity.
Mechanistically, we identify Usp12 as a potent inducer of
neuronal autophagy. Usp12 overexpression accelerates
autophagic flux and induces an approximately sixfold
increase in autophagic structures as determined by
ultrastructural analyses, while suppression of endogenous
Usp12 slows autophagy. Surprisingly, the catalytic activity
of Usp12 is not required to protect against
neurodegeneration or induce autophagy. These findings
identify the deubiquitinase Usp12 as a regulator of neuronal
proteostasis and mHTT-mediated neurodegeneration.},
cin = {G160},
ddc = {500},
cid = {I:(DE-He78)G160-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30266909},
pmc = {pmc:PMC6162324},
doi = {10.1038/s41467-018-05653-z},
url = {https://inrepo02.dkfz.de/record/141978},
}