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@ARTICLE{Sharma:153373,
author = {Sharma, Amit and Liu, Hongde and Tobar-Tosse, Fabian and
Chand Dakal, Tikam and Ludwig, Michael and Holz, Frank G and
Loeffler, Karin U and Wüllner, Ullrich and Herwig-Carl,
Martina C},
title = {{U}biquitin {C}arboxyl-{T}erminal {H}ydrolases ({UCH}s):
{P}otential {M}ediators for {C}ancer and
{N}eurodegeneration.},
journal = {International journal of molecular sciences},
volume = {21},
number = {11},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2020-01370},
pages = {3910 -},
year = {2020},
abstract = {Emerging evidence suggests an inverse association between
cancer and neurodegenerative diseases (NDD). Although
phenotypically different, both diseases display a
significant imbalance in the ubiquitination/deubiquitination
processes. Therefore, we particularly investigated the
expression of ubiquitin C-terminal hydrolases (UCHs: UCH-L1,
UCH-L3, UCH-L5 and BAP1), a subfamily of deubiquitinating
enzymes (DUBs), using publically available datasets (GTEx,
TCGA) and observed altered expression of UCH-L1, UCH-L3,
UCH-L5 in 17 cancer types. Interestingly, UCH-L1 (known to
be enriched in neurons and interacting with the Parkinson's
disease-associated protein α-synuclein) appeared to be a
prognostic indicator of unfavorable outcome in endometrial
and urothelial cancer, while increased expression of UCH-L3
and UCH-L5 was associated with poor survival in liver and
thyroid cancer, respectively. In normal tissues, UCH-L1 was
found to be strongly expressed in the cerebral cortex and
hypothalamus, while UCH-L3 expression was somewhat higher in
the testis. The occurrence of mutation rates in UCHs also
suggests that BAP1 and UCH-L5 may play a more dominant role
in cancers than UCH-L1 and UCH-L3. We also characterized the
functional context and configuration of the repeat elements
in the promoter of DUBs genes and found that UCHs are highly
discriminatory for catabolic function and are mainly
enriched with LINE/CR1 repeats. Regarding the thesis of an
inverse association between cancer and NDD, we observed that
among all DUBs, UCHs are the one most involved in both
entities. Considering a putative therapeutic potential based
on presumed common mechanisms, it will be useful to
determine whether other DUBs can compensate for the loss of
UCH activity under physiological conditions. However,
experimental evidence is required to substantiate this
argument.},
keywords = {Brain: metabolism / Databases, Genetic / Gene Expression
Profiling / Gene Expression Regulation / Humans / Neoplasms:
enzymology / Neurodegenerative Diseases: enzymology /
Phenotype / Prognosis / Protein Domains / Tumor Suppressor
Proteins: metabolism / Ubiquitin Thiolesterase: genetics /
Ubiquitin Thiolesterase: metabolism / Ubiquitination},
cin = {AG Wüllner ; AG Wüllner 2},
ddc = {540},
cid = {I:(DE-2719)1011302},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32486284},
pmc = {pmc:PMC7312489},
doi = {10.3390/ijms21113910},
url = {https://pub.dzne.de/record/153373},
}