Dysregulation
of
CD4+
T
cell
differentiation
is
linked
to
autoimmune
diseases.
Metabolic
reprogramming
from
oxidative
phosphorylation
glycolysis
and
accumulation
lactate
are
involved
in
this
process.
However,
the
underlying
mechanisms
remain
unclear.
Our
study
showed
that
lactate-derived
lactylation
regulated
differentiation.
Lactylation
levels
cells
increased
with
progression
experimental
uveitis
(EAU).
Inhibition
suppressed
TH17
attenuated
EAU
inflammation.
The
global
lactylome
revealed
landscape
lactylated
sites
proteins
normal
mice.
Specifically,
hyperlactylation
Ikzf1
at
Lys164
promoted
by
directly
modulating
expression
TH17-related
genes,
including
Runx1,
Tlr4,
interleukin-2
(IL-2),
IL-4.
Delactylation
impaired
These
findings
exemplify
how
regulates
site
specificity
protein
promote
implicate
as
a
potential
therapeutic
target
for
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Сен. 1, 2022
Abstract
The
current
understanding
of
lactate
extends
from
its
origins
as
a
byproduct
glycolysis
to
role
in
tumor
metabolism,
identified
by
studies
on
the
Warburg
effect.
shuttle
hypothesis
suggests
that
plays
an
important
bridging
signaling
molecule
coordinates
among
different
cells,
organs
and
tissues.
Lactylation
is
posttranslational
modification
initially
reported
Professor
Yingming
Zhao’s
research
group
2019.
Subsequent
confirmed
lactylation
vital
component
function
involved
proliferation,
neural
excitation,
inflammation
other
biological
processes.
An
indispensable
substance
for
various
physiological
cellular
functions,
regulatory
aspects
energy
metabolism
signal
transduction.
Therefore,
comprehensive
review
summary
presented
clarify
disease
provide
reference
direction
future
research.
This
offers
systematic
overview
homeostasis
roles
pathological
processes,
well
effects
diseases,
particularly
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Март 17, 2023
Abstract
Chronic
kidney
disease
(CKD)
is
estimated
to
affect
10–14%
of
global
population.
Kidney
fibrosis,
characterized
by
excessive
extracellular
matrix
deposition
leading
scarring,
a
hallmark
manifestation
in
different
progressive
CKD;
However,
at
present
no
antifibrotic
therapies
against
CKD
exist.
fibrosis
identified
tubule
atrophy,
interstitial
chronic
inflammation
and
fibrogenesis,
glomerulosclerosis,
vascular
rarefaction.
Fibrotic
niche,
where
organ
initiates,
complex
interplay
between
injured
parenchyma
(like
tubular
cells)
multiple
non-parenchymal
cell
lineages
(immune
mesenchymal
located
spatially
within
scarring
areas.
Although
the
mechanisms
are
complicated
due
kinds
cells
involved,
with
help
single-cell
technology,
many
key
questions
have
been
explored,
such
as
what
kind
renal
tubules
profibrotic,
myofibroblasts
originate,
which
immune
how
communicate
each
other.
In
addition,
genetics
epigenetics
deeper
that
regulate
fibrosis.
And
reversible
nature
epigenetic
changes
including
DNA
methylation,
RNA
interference,
chromatin
remodeling,
gives
an
opportunity
stop
or
reverse
therapeutic
strategies.
More
marketed
(e.g.,
RAS
blockage,
SGLT2
inhibitors)
developed
delay
progression
recent
years.
Furthermore,
better
understanding
also
favored
discover
biomarkers
fibrotic
injury.
review,
we
update
advances
mechanism
summarize
novel
treatment
for
CKD.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Март 2, 2023
Abstract
Epigenetics
regulates
gene
expression
and
has
been
confirmed
to
play
a
critical
role
in
variety
of
metabolic
diseases,
such
as
diabetes,
obesity,
non-alcoholic
fatty
liver
disease
(NAFLD),
osteoporosis,
gout,
hyperthyroidism,
hypothyroidism
others.
The
term
‘epigenetics’
was
firstly
proposed
1942
with
the
development
technologies,
exploration
epigenetics
made
great
progresses.
There
are
four
main
epigenetic
mechanisms,
including
DNA
methylation,
histone
modification,
chromatin
remodelling,
noncoding
RNA
(ncRNA),
which
exert
different
effects
on
diseases.
Genetic
non-genetic
factors,
ageing,
diet,
exercise,
interact
jointly
affect
formation
phenotype.
Understanding
could
be
applied
diagnosing
treating
diseases
clinic,
biomarkers,
drugs,
editing.
In
this
review,
we
introduce
brief
history
well
milestone
events
since
proposal
‘epigenetics’.
Moreover,
summarise
research
methods
general
mechanisms
modulation.
Furthermore,
interaction
between
genetic
or
factors.
Finally,
clinical
trials
applications
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Фев. 17, 2023
Abstract
Drug
resistance
is
mainly
responsible
for
cancer
recurrence
and
poor
prognosis.
Epigenetic
regulation
a
heritable
change
in
gene
expressions
independent
of
nucleotide
sequence
changes.
As
the
common
epigenetic
mechanisms,
DNA
methylation,
histone
modification,
non-coding
RNA
have
been
well
studied.
Increasing
evidence
has
shown
that
aberrant
regulations
contribute
to
tumor
resistance.
Therefore,
targeting
regulators
represents
an
effective
strategy
reverse
drug
In
this
review,
we
summarize
roles
addition,
as
essential
factors
modifications,
demethylases
mediate
or
genomic
modifications.
Herein,
comprehensively
describe
functions
demethylase
family
including
lysine-specific
family,
Jumonji
C-domain-containing
arginine
fully
discuss
their
regulatory
mechanisms
related
therapeutic
strategies,
small-molecule
inhibitors
small
interfering
overcome
resistance,
are
also
described.
Protein
posttranslational
modifications
(PTMs)
refer
to
the
breaking
or
generation
of
covalent
bonds
on
backbones
amino
acid
side
chains
proteins
and
expand
diversity
proteins,
which
provides
basis
for
emergence
organismal
complexity.
To
date,
more
than
650
types
protein
modifications,
such
as
most
well-known
phosphorylation,
ubiquitination,
glycosylation,
methylation,
SUMOylation,
short-chain
long-chain
acylation
redox
irreversible
have
been
described,
inventory
is
still
increasing.
By
changing
conformation,
localization,
activity,
stability,
charges,
interactions
with
other
biomolecules,
PTMs
ultimately
alter
phenotypes
biological
processes
cells.
The
homeostasis
important
human
health.
Abnormal
may
cause
changes
in
properties
loss
functions,
are
closely
related
occurrence
development
various
diseases.
In
this
review,
we
systematically
introduce
characteristics,
regulatory
mechanisms,
functions
health
addition,
therapeutic
prospects
diseases
by
targeting
associated
enzymes
also
summarized.
This
work
will
deepen
understanding
promote
discovery
diagnostic
prognostic
markers
drug
targets
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Дек. 29, 2022
Metabolic
reprogramming
is
involved
in
the
pathogenesis
of
not
only
cancers
but
also
neurodegenerative
diseases,
cardiovascular
and
infectious
diseases.
With
progress
metabonomics
proteomics,
metabolites
have
been
found
to
affect
protein
acylations
through
providing
acyl
groups
or
changing
activities
acyltransferases
deacylases.
Reciprocally,
acylation
key
cellular
processes
relevant
physiology
such
as
stability,
subcellular
localization,
enzyme
activity,
transcriptional
protein-protein
interactions
protein-DNA
interactions.
Herein,
we
summarize
functional
diversity
mechanisms
eight
kinds
nonhistone
physiological
progression
several
We
highlight
recent
development
inhibitors
for
acyltransferase,
deacylase,
reader
proteins
their
potential
applications
drug
discovery.
Abstract
Epigenome
reprogramming
after
fertilization
enables
transcriptionally
quiescent
maternal
and
paternal
chromatin
to
acquire
a
permissive
state
for
subsequent
zygotic
genome
activation
(ZGA).
H3K27
acetylation
(H3K27ac)
is
well‐established
marker
of
active
enhancers
promoters.
However,
dynamics
H3K27ac
during
maternal‐to‐zygotic
transition
(MZT)
in
mammalian
embryos
are
not
well‐studied.
By
profiling
the
allelic
landscape
mouse
MZT,
we
show
that
undergoes
three
waves
rapid
global
transitions
between
oocyte
stage
2‐cell
stage.
Notably,
germinal
vesicle
zygote
globally
hyperacetylated,
with
noncanonical,
broad
domains
correlate
H3K4
trimethylation
(H3K4me3)
open
chromatin.
marks
genomic
regions
primed
including
ZGA
genes,
retrotransposons,
alleles
imprinted
genes.
We
CBP/p300
HDAC
activities
play
important
roles
regulating
essential
preimplantation
development.
Specifically,
acetyltransferase
broadly
deposits
zygotes
induce
opening
condensed
at
putative
ensure
proper
ZGA.
On
contrary,
HDACs
revert
canonical
safeguard
by
preventing
premature
expression
developmental
In
conclusion,
coordinated
MZT
