Wound
response
programs
are
often
activated
during
neoplastic
growth
in
tumors.
In
both
wound
repair
and
tumor
growth,
cells
respond
to
acute
stress
balance
the
activation
of
multiple
programs,
including
apoptosis,
proliferation,
cell
migration.
Central
those
responses
JNK/MAPK
JAK/STAT
signaling
pathways.
Yet,
what
extent
these
cascades
interact
at
cis-regulatory
level
how
they
orchestrate
different
regulatory
phenotypic
is
still
unclear.
Here,
we
aim
characterize
states
that
emerge
cooperate
response,
using
Drosophila
melanogaster
wing
disc
as
a
model
system,
compare
with
cancer
induced
by
rasV12scrib-/-
eye
disc.
We
used
single-cell
multiome
profiling
derive
enhancer
gene
networks
(eGRNs)
integrating
chromatin
accessibility
expression
signals.
identify
'proliferative'
eGRN,
active
majority
wounded
controlled
AP-1
STAT.
smaller,
but
distinct
population
cells,
'senescent'
eGRN
driven
C/EBP-like
transcription
factors
(Irbp18,
Xrp1,
Slow
border,
Vrille)
Scalloped.
These
two
signatures
found
be
levels.
Our
eGRNs
resource
offers
an
in-depth
characterization
senescence
markers,
together
new
perspective
on
shared
acting
oncogenesis.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 23, 2024
Abstract
Protein
translation
is
a
tightly
regulated
cellular
process
that
essential
for
gene
expression
and
protein
synthesis.
The
deregulation
of
this
increasingly
recognized
as
critical
factor
in
the
pathogenesis
various
human
diseases.
In
review,
we
discuss
how
deregulated
can
lead
to
aberrant
synthesis,
altered
functions,
disease
progression.
We
explore
key
mechanisms
contributing
translation,
including
functional
alterations
factors,
tRNA,
mRNA,
ribosome
function.
Deregulated
leads
abnormal
expression,
disrupted
signaling,
perturbed
functions-
all
which
contribute
pathogenesis.
development
profiling
techniques
along
with
mass
spectrometry-based
proteomics,
mRNA
sequencing
single-cell
approaches
have
opened
new
avenues
detecting
diseases
related
errors.
Importantly,
highlight
recent
advances
therapies
targeting
translation-related
disorders
their
potential
applications
neurodegenerative
diseases,
cancer,
infectious
cardiovascular
Moreover,
growing
interest
lies
targeted
aimed
at
restoring
precise
control
over
diseased
cells
discussed.
conclusion,
comprehensive
review
underscores
role
its
therapeutic
target.
Advancements
understanding
molecular
deregulation,
coupled
therapies,
offer
promising
improving
outcomes
Additionally,
it
will
unlock
doors
possibility
precision
medicine
by
offering
personalized
deeper
underpinnings
future.
ABSTRACT
Although
differential
transcription
drives
the
development
of
multicellular
organisms,
ultimate
readout
a
protein-coding
gene
is
ribosome-dependent
mRNA
translation.
Ribosomes
were
once
thought
as
uniform
molecular
machines,
but
emerging
evidence
indicates
that
complexity
and
diversity
ribosome
biogenesis
function
should
be
given
fresh
look
in
context
development.
This
Review
begins
with
discussion
different
developmental
disorders
have
been
linked
perturbations
production
function.
We
then
highlight
recent
studies
reveal
how
cells
tissues
exhibit
variable
levels
protein
synthesis,
changes
synthesis
capacity
can
influence
specific
cell
fate
decisions.
finish
by
touching
upon
heterogeneity
stress
responses
These
discussions
importance
considering
both
functional
specialization
disease.
The
elimination
of
unfit
cells
from
a
tissue
is
process
known
in
Drosophila
and
mammals
as
cell
competition.
In
well-studied
paradigm
"loser"
that
are
heterozygous
mutant
for
haploinsufficient
ribosomal
protein
gene
eliminated
developing
tissues
via
apoptosis
when
surrounded
by
fitter
wild-type
cells,
referred
to
"winner"
cells.
However,
the
mechanisms
underlying
induction
this
phenomenon
not
fully
understood.
Here
we
report
CCAAT-Enhancer-Binding
Protein
(C/EBP),
Xrp1,
which
help
maintaining
genomic
stability
after
genotoxic
stress,
necessary
loser
clones
Xrp1
transcriptionally
upregulated
an
autoregulatory
loop
able
trigger
-
driving
elimination.
We
further
show
acts
nucleus
regulate
transcription
several
genes
have
been
previously
involved
therefore
speculate
might
play
fundamental
role
molecular
caretaker
integrity
tissues.
Development Growth & Differentiation,
Год журнала:
2018,
Номер
60(9), С. 522 - 530
Опубликована: Ноя. 15, 2018
Cell
competition
is
a
context-dependent
cell
elimination
through
short-range
cell-cell
interaction,
in
which
cells
with
higher
fitness
eliminate
neighboring
less-fit
or
oncogenic
within
the
growing
tissue.
can
be
triggered
by
many
different
factors
such
as
heterozygous
mutations
ribosomal
protein
genes
(which
are
called
"Minute"
mutations),
elevated
Myc,
Yorkie/YAP,
Wg/Wnt,
JAK-STAT,
Ras,
Src
activity,
and
loss
of
Mahjong/VprBP,
endocytic
pathway
components,
apicobasal
polarity.
Studies
on
mechanisms
roles
have
suggested
that
divided
into
two
types:
selection
fitter
cells.
The
former
type
includes
Minute
Myc-induced
considered
to
dependent
relative
level
synthesis.
later
tumor-suppressive
polarity
scribble
(scrib)
discs
large
(dlg).
Genetic
studies
Drosophila
during
past
decade
provided
significant
progress
understanding
these
phenomena.
At
same
time,
now
raised
new
questions;
how
do
contribute
cooperate
drive
competition,
common
exist
types
what
physiological
phenomena?
