ABSTRACT
Daily
rhythms
in
the
rate
and
specificity
of
protein
synthesis
occur
most
mammalian
cells
through
an
interaction
between
cell‐autonomous
circadian
regulation
daily
cycles
systemic
cues.
However,
overall
content
a
typical
cell
changes
little
over
24
h.
For
proteins,
translation
appears
to
be
coordinated
with
degradation,
producing
phases
proteomic
renewal
that
maximize
energy
efficiency
while
broadly
maintaining
proteostasis
across
solar
cycle.
We
propose
major
function
this
temporal
compartmentalization—and
rhythmicity
general—is
optimize
associated
processes
such
as
complex
assembly.
further
much
compartmentalization
is
achieved
at
level
translational
initiation,
machinery
alternates
distinct
mechanisms,
each
using
toolkit
phosphoproteins
preferentially
recognize
translate
different
classes
mRNA.
Current Opinion in Neurobiology,
Год журнала:
2024,
Номер
87, С. 102886 - 102886
Опубликована: Июнь 19, 2024
The
integrated
stress
response
(ISR)
is
a
highly
conserved
biochemical
pathway
that
regulates
protein
synthesis.
ISR
activated
in
to
diverse
stressors
restore
cellular
homeostasis.
As
such,
the
implicated
wide
range
of
diseases,
including
brain
disorders.
However,
brain,
also
has
potent
influence
on
processes
beyond
proteostasis,
namely
synaptic
plasticity,
learning
and
memory.
Thus,
setting
activity
may
have
dual
effects
proteostasis
function.
In
this
review,
we
consider
ISR's
contribution
disorders
through
lens
its
potential
plasticity.
From
these
examples,
illustrate
at
times
be
"double-edged
sword".
We
highlight
as
therapeutic
target
improve
circuit
function
diseases
independent
role
disease
pathogenesis.
Biomolecules,
Год журнала:
2025,
Номер
15(2), С. 248 - 248
Опубликована: Фев. 8, 2025
The
type
I
protein
kinase
PERK
is
an
endoplasmic
reticulum
(ER)
transmembrane
that
plays
a
multifaceted
role
in
cancer
development
and
progression,
influencing
tumor
growth,
metastasis,
cellular
stress
responses.
activation
of
represents
one
the
three
signaling
pathways
induced
during
unfolded
response
(UPR),
which
triggered,
particular,
cells
constitutively
experience
various
intracellular
extracellular
stresses
impair
folding
within
ER.
can
lead
to
both
pro-survival
proapoptotic
outcomes,
depending
on
context
extent
ER
stress.
It
helps
reprogramming
gene
expression
cells,
thereby
ensuring
survival
face
oncogenic
stress,
such
as
replicative
DNA
damage,
also
microenvironmental
challenges,
including
hypoxia,
angiogenesis,
metastasis.
Consequently,
contributes
initiation,
transformation,
adaptation
microenvironment,
chemoresistance.
However,
sustained
cell
proliferation
promote
apoptotic
death
by
interconnected
processes,
mitochondrial
dysfunction,
translational
inhibition,
accumulation
stresses,
specific
induction
multifunctional
factors,
CHOP.
dual
promoting
progression
suppression
makes
it
complex
target
for
therapeutic
interventions.
A
comprehensive
understanding
intricacies
pathway
their
impact
essential
effective
strategies,
particularly
diseases
like
cancer,
where
deregulated
most,
if
not
all,
solid
liquid
tumors.
This
article
provides
overview
knowledge
acquired
from
study
animal
models
lines
cultured
vitro
PERK’s
functions
thus
highlighting
potential
new
avenues
could
this
protein.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2025,
Номер
44(1)
Опубликована: Фев. 13, 2025
Abstract
Background
Glucose
metabolism
plays
a
critical
role
in
tumor
progression.
When
glucose
intake
is
insufficient
and
the
tumor’s
growth
rate
exceeds
its
energy
supply,
cells
typically
adapt
overcome
stress
through
compensatory
mechanisms
to
maintain
survival
of
cells,
which
may
also
be
related
recurrence
or
metastasis.
Methods
Different
concentrations
were
selected
as
basis
for
model
gastric
cancer.
Then
CCK-8
flow
cytometry
used
detect
effects
on
cell
proliferation,
apoptosis,
cycle.
Differentially
expressed
genes
(DEGs)
screened
by
RNA
sequencing
regulated
pathways
identified
gene
set
enrichment
analysis.
The
regulatory
relationship
between
PPP1R15A
transcription
factor
JUN
was
proved
ChIP-qPCR
dual-luciferase
reporter
assay.
gain
loss
function
assays
conducted
examine
under
vivo
vitro.
Potential
further
analyzed
combination
online
databases,
sequencing,
metabolite
sequencing.
regulation
autophagy
detected
western
blot,
transmission
electron
microscope,
mRFP-GFP-LC3
adenovirus
laser
scanning
confocal
microscopy.
Results
significantly
upregulated
deprivation
(0
mM
vs.
25
mM),
combined
with
promoter
activated
expression.
Both
highly
cancer
tissues
independent
risk
factors
prognosis
cohort.
Overexpression
promoted
inhibited
involved
cycle
arrest.
Further
suggested
that
associated
autophagy.
In
vitro
experiments
confirmed
both
overexpression
biosynthesis
autolysosome
autophagosome,
cleavage
LC3
complex
cells.
Moreover,
knockdown
induced
deprivation.
Conclusions
sustained
regulating
resist
harsh
environments.
PLoS Pathogens,
Год журнала:
2025,
Номер
21(2), С. e1012934 - e1012934
Опубликована: Фев. 14, 2025
EBV
infects
normal
oral
keratinocytes
(NOKs)
and
plays
an
essential
role
in
undifferentiated
nasopharyngeal
carcinoma
(NPC).
We
previously
showed
that
the
oncogene,
LMP1,
promotes
proliferation
inhibits
spontaneous
differentiation
telomerase-immortalized
NOKs
grown
growth
factor-restricted
conditions.
Here
we
have
further
examined
phenotypes
of
infected
with
wild-type
(WT
EBV)
versus
LMP1-deleted
mutant
(ΔLMP1
RNA-seq
results
show
WT
EBV-infected
not
only
reduced
differentiation,
but
also
decreased
expression
genes
activated
by
integrated
stress
response
(ISR)
pathway,
comparison
to
ΔLMP1
cells.
The
ISR
pathway
is
mediated
increased
phosphorylation
eIF2α
translation
initiation
factor,
leading
most
cellular
proteins
some
proteins,
including
ATF4
CHOP.
Immunoblot
analyses
confirmed
uninfected
cells
LMP1
alone
sufficient
inhibit
phosphorylation.
found
decreases
activity
two
different
kinases,
PERK
GCN2,
NOKs,
resulting
ISR-induced
transcription
factors,
CHOP,
NOKs.
Furthermore,
both
GCN2
are
required
for
efficient
TPA-induced
lytic
reactivation
TPA-mediated
epithelial
cell
differentiation.
In
addition,
demonstrate
over-expression
CHOP
induce
NPC
this
effect
activation
differentiation-inducing
KLF4
BLIMP1.
Our
suggest
inhibition
oncoprotein,
may
promote
early
development
preventing
reactivation.
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(5), С. 4885 - 4923
Опубликована: Май 17, 2024
Cold
plasma
(CP)
is
an
ionised
gas
containing
excited
molecules
and
ions,
radicals,
free
electrons,
which
emits
electric
fields
UV
radiation.
CP
potently
antimicrobial,
can
be
applied
safely
to
biological
tissue,
birthing
the
field
of
medicine.
Reactive
oxygen
nitrogen
species
(RONS)
produced
by
affect
processes
directly
or
indirectly
via
modification
cellular
lipids,
proteins,
DNA,
intracellular
signalling
pathways.
at
lower
levels
for
oxidative
eustress
activate
cell
proliferation,
motility,
migration,
antioxidant
production
in
normal
cells,
mainly
potentiated
unfolded
protein
response,
nuclear
factor-erythroid
factor
2-related
2
(Nrf2)-activated
response
element,
phosphoinositide
3-kinase/protein
kinase
B
(PI3K/Akt)
pathway,
also
activates
factor-kappa
(NFκB).
At
higher
exposures,
inactivation,
apoptosis,
autophagy
malignant
cells
occur
degradation
PI3K/Akt
mitogen-activated
(MAPK)-dependent
-independent
activation
master
tumour
suppressor
p53,
leading
caspase-mediated
death.
These
opposing
responses
validate
a
hormesis
approach
Clinical
applications
are
becoming
increasingly
realised
wound
healing,
while
clinical
effectiveness
tumours
currently
coming
light.
This
review
will
outline
advances
medicine
compare
main
redox
healing
cancer.
