Nature Communications,
Год журнала:
2017,
Номер
8(1)
Опубликована: Фев. 15, 2017
Abstract
ETS
transcription
factors
are
commonly
deregulated
in
cancer
by
chromosomal
translocation,
overexpression
or
post-translational
modification
to
induce
gene
expression
programs
essential
tumorigenicity.
Targeted
destruction
of
these
proteins
may
have
therapeutic
impact.
Here
we
report
that
Ets-1
is
regulated
the
deubiquitinating
enzyme,
Usp9x,
and
has
major
impact
on
tumorigenic
program
metastatic
melanoma.
deubiquitination
blocks
its
proteasomal
enhances
tumorigenicity,
which
could
be
reversed
Usp9x
knockdown
inhibition.
levels
coincidently
elevated
melanoma
with
highest
detected
tumours
versus
normal
skin
benign
lesions.
Notably,
induced
BRAF
MEK
kinase
inhibition,
resulting
increased
NRAS
expression,
blocked
inactivation
combination
inhibitor
fully
suppressed
growth.
Thus,
modulates
Ets-1/NRAS
regulatory
network
biologic
implications.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2023,
Номер
42(1)
Опубликована: Сен. 1, 2023
Tumors
have
evolved
in
various
mechanisms
to
evade
the
immune
system,
hindering
antitumor
response
and
facilitating
tumor
progression.
Immunotherapy
has
become
a
potential
treatment
strategy
specific
different
cancer
types
by
utilizing
multifarious
molecular
enhance
against
tumors.
Among
these
mechanisms,
ubiquitin-proteasome
system
(UPS)
is
significant
non-lysosomal
pathway
protein
degradation,
regulated
deubiquitinating
enzymes
(DUBs)
that
counterbalance
ubiquitin
signaling.
Ubiquitin-specific
proteases
(USPs),
largest
DUB
family
with
strongest
variety,
play
critical
roles
modulating
cell
function,
regulating
response,
participating
antigen
processing
presentation
during
According
recent
studies,
expressions
of
some
USP
members
cells
are
involved
escape
microenvironment.
This
review
explores
targeting
USPs
as
new
approach
for
immunotherapy,
highlighting
basic
preclinical
studies
investigating
applications
inhibitors.
By
providing
insights
into
structure
function
immunity,
this
aims
at
assisting
developing
therapeutic
approaches
enhancing
immunotherapy
efficacy.
Nature Communications,
Год журнала:
2017,
Номер
8(1)
Опубликована: Март 31, 2017
Abstract
Defective
centrosome
duplication
is
implicated
in
microcephaly
and
primordial
dwarfism
as
well
various
ciliopathies
cancers.
Yet,
how
the
biogenesis
regulated
remains
poorly
understood.
Here
we
report
that
X-linked
deubiquitinase
USP9X
physically
associated
with
centriolar
satellite
protein
CEP131,
thereby
stabilizing
CEP131
through
its
activity.
We
demonstrate
an
integral
component
of
required
for
biogenesis.
Loss-of-function
impairs
gain-of-function
promotes
amplification
chromosome
instability.
Significantly,
overexpressed
breast
carcinomas,
level
expression
correlated
higher
histologic
grades
cancer.
Indeed,
USP9X,
regulation
abundance,
carcinogenesis.
Our
experiments
identify
important
regulator
uncover
a
critical
role
USP9X/CEP131
carcinogenesis,
supporting
pursuit
potential
targets
cancer
intervention.
Cancers,
Год журнала:
2020,
Номер
12(6), С. 1579 - 1579
Опубликована: Июнь 15, 2020
Since
the
discovery
of
ubiquitin
proteasome
system
(UPS),
roles
ubiquitinating
and
deubiquitinating
enzymes
(DUBs)
have
been
widely
elucidated.
The
ubiquitination
proteins
regulates
many
aspects
cellular
functions
such
as
protein
degradation
localization,
also
modifies
protein-protein
interactions.
DUBs
cleave
attached
moieties
from
substrates
thereby
reverse
process
ubiquitination.
dysregulation
these
two
paramount
pathways
has
implicated
in
numerous
diseases,
including
cancer.
Attempts
are
being
made
to
identify
inhibitors
E3
ligases
that
potentially
clinical
implications
cancer,
making
them
an
important
target
pharmaceutical
industry.
Therefore,
studies
medicine
currently
focused
on
pharmacological
disruption
DUB
activity
a
rationale
specifically
cancer-causing
aberrations.
Here,
we
briefly
discuss
pathophysiological
physiological
key
cancer-related
pathways.
We
applications
promising
may
contribute
development
therapeutic
targets
future.
Molecular Therapy,
Год журнала:
2021,
Номер
29(3), С. 908 - 919
Опубликована: Янв. 1, 2021
A
growing
amount
of
evidence
suggests
that
ubiquitination
and
deubiquitination
programmed
death
1
(PD-1)/programmed
death-ligand
(PD-L1)
play
crucial
roles
in
the
regulation
PD-1
PD-L1
protein
stabilization
dynamics.
PD-1/PD-L1
is
a
major
coinhibitory
checkpoint
pathway
modulates
immune
escape
cancer
patients,
its
engagement
inhibition
has
significantly
reshaped
landscape
tumor
clearance.
The
abnormal
influence
PD-1/PD-L1-mediated
immunosuppression.
In
this
review,
we
describe
ubiquitination-
deubiquitination-mediated
modulation
signaling
through
variety
E3
ligases
deubiquitinating
enzymes
(DUBs).
Moreover,
briefly
expound
on
anticancer
potential
some
agents
target
related
ligases,
which
further
modulate
cancers.
Therefore,
review
reveals
development
highly
promising
therapeutic
approach
for
immunotherapy
by
targeting
ubiquitination.
Journal of Clinical Investigation,
Год журнала:
2019,
Номер
129(5), С. 2043 - 2055
Опубликована: Апрель 7, 2019
The
mesenchymal
(MES)
subtype
of
glioblastoma
(GBM)
stem
cells
(GSCs)
represents
a
subpopulation
cancer
that
are
notorious
for
their
highly
aggressive
nature
and
resistance
to
conventional
therapy.
Aldehyde
dehydrogenase
1A3
(ALDH1A3)
has
been
recently
suggested
as
key
determinant
the
maintenance
MES
features
GSCs.
However,
mechanisms
underpinning
aberrant
ALDH1A3
expression
remain
elusive.
Here,
we
identified
ubiquitin-specific
protease
9X
(USP9X)
bona
fide
deubiquitinase
in
USP9X
interacted
with,
depolyubiquitylated,
stabilized
ALDH1A3.
Moreover,
showed
FACS-sorted
USP9Xhi
were
enriched
GSCs
with
high
activity
potent
tumorigenic
capacity.
Depletion
markedly
downregulated
ALDH1A3,
resulting
loss
self-renewal
capacity
GSCs,
which
could
be
largely
rescued
by
ectopic
Furthermore,
demonstrated
inhibitor
WP1130
induced
degradation
marked
therapeutic
efficacy
GSC–derived
orthotopic
xenograft
models.
Additionally,
strongly
correlated
primary
human
GBM
samples
had
prognostic
value
patients
subgroup.
Collectively,
our
findings
unveil
protein
stabilization
potential
target
GSC-directed