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@ARTICLE{Schwintzer:140619,
author = {Schwintzer, Lukas and Aguado Roca, Eva and Broemer, Meike},
title = {{TRIAD}3/{RNF}216 {E}3 ligase specifically synthesises
{K}63-linked ubiquitin chains and is inactivated by
mutations associated with {G}ordon {H}olmes syndrome.},
journal = {Cell death discovery},
volume = {5},
number = {1},
issn = {2058-7716},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DZNE-2020-06941},
pages = {75},
year = {2019},
abstract = {TRIAD3/RNF216 is a ubiquitin ligase of the
RING-in-between-RING family. Recent publications identified
TRIAD3 mutations in patients with neurological diseases,
including Gordon Holmes syndrome and Huntington-like
disorder. To understand the functional relevance of these
disease-associated mutations, we have tested the ubiquitin
ligase activity of mutated TRIAD3 in vitro. Several of these
point mutations completely abrogated TRIAD3's catalytic
activity. Using mass spectrometry, we identified new
TRIAD3-interacting proteins/substrates from mouse brain
lysate, which provide a new link between TRIAD3 and
processes involving clathrin-mediated endocytosis.
Strikingly, we found that TRIAD3 synthesises specifically
lysine-63 (K63)-linked poly-ubiquitin chains in vitro, a
chain type that usually plays a role in mediating signalling
events rather than triggering proteasomal degradation.
Therefore, this finding is of great importance to further
understand TRIAD3's cellular role and loss-of-function in
disease.},
cin = {AG Brömer 1},
ddc = {610},
cid = {I:(DE-2719)5000021},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30886743},
pmc = {pmc:PMC6411869},
doi = {10.1038/s41420-019-0158-6},
url = {https://pub.dzne.de/record/140619},
}