Life,
Journal Year:
2025,
Volume and Issue:
15(4), P. 655 - 655
Published: April 16, 2025
Protein
kinase
A
(PKA)
is
a
key
regulator
of
cellular
signaling
that
regulates
physiological
processes
such
as
metabolism,
cell
proliferation,
and
neuronal
function.
While
its
activation
by
the
second
messenger
3′,5′-cyclic
adenosine
triphosphate
(cAMP)
well
characterized,
recent
research
highlights
additional
regulatory
mechanisms,
particularly
oxidative
post-translational
modifications,
influence
PKA’s
structure,
activity,
substrate
specificity.
Both
catalytic
subunits
PKA
are
susceptible
to
redox
which
have
been
shown
play
important
roles
in
regulation
functions,
including
cardiac
contractility,
lipid
immune
response.
Likewise,
redox-dependent
modulation
has
implicated
numerous
diseases,
cardiovascular
disorders,
diabetes,
neurodegenerative
conditions,
making
it
potential
therapeutic
target.
However,
mechanisms
crosstalk
between
redox-
PKA-dependent
remain
poorly
understood.
This
review
examines
structural
functional
PKA,
with
focus
on
modifications
their
impact
signaling.
deeper
understanding
these
may
provide
new
strategies
for
targeting
stress
disease
restoring
balanced
cells.
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: June 30, 2023
Divergent
N6-methyladenosine
(m6A)
modifications
are
dynamic
and
reversible
posttranscriptional
RNA
that
mediated
by
m6A
regulators
or
methylation
regulators,
i.e.,
methyltransferases
("writers"),
demethylases
("erasers"),
m6A-binding
proteins
("readers").
Aberrant
associated
with
cancer
occurrence,
development,
progression,
prognosis.
Numerous
studies
have
established
aberrant
function
as
either
tumor
suppressors
oncogenes
in
multiple
types.
However,
the
functions
mechanisms
of
remain
largely
elusive
should
be
explored.
Emerging
suggest
can
modulated
epigenetic
modifications,
namely,
ubiquitination,
SUMOylation,
acetylation,
methylation,
phosphorylation,
O-GlcNAcylation,
ISGylation,
lactylation
via
noncoding
action,
cancer.
This
review
summarizes
current
roles
The
for
modification
genesis
segregated.
will
improve
understanding
regulatory
regulators.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Dec. 10, 2023
Abstract
Ferroptosis,
a
unique
modality
of
cell
death
with
mechanistic
and
morphological
differences
from
other
modes,
plays
pivotal
role
in
regulating
tumorigenesis
offers
new
opportunity
for
modulating
anticancer
drug
resistance.
Aberrant
epigenetic
modifications
posttranslational
(PTMs)
promote
resistance,
cancer
progression,
metastasis.
Accumulating
studies
indicate
that
can
transcriptionally
translationally
determine
vulnerability
to
ferroptosis
functions
as
driver
nervous
system
diseases
(NSDs),
cardiovascular
(CVDs),
liver
diseases,
lung
kidney
diseases.
In
this
review,
we
first
summarize
the
core
molecular
mechanisms
ferroptosis.
Then,
roles
processes,
including
histone
PTMs,
DNA
methylation,
noncoding
RNA
regulation
such
phosphorylation,
ubiquitination,
SUMOylation,
acetylation,
ADP-ribosylation,
are
concisely
discussed.
The
PTMs
genesis
cancers,
NSD,
CVDs,
well
application
PTM
modulators
therapy
these
then
discussed
detail.
Elucidating
mediated
by
will
facilitate
development
promising
combination
therapeutic
regimens
containing
or
PTM-targeting
agents
inducers
be
used
overcome
chemotherapeutic
resistance
could
prevent
addition,
highlight
potential
approaches
chemoresistance
halt
Chemical Reviews,
Journal Year:
2024,
Volume and Issue:
124(5), P. 2805 - 2838
Published: Feb. 19, 2024
Post-translational
modifications
(PTMs)
endow
proteins
with
new
properties
to
respond
environmental
changes
or
growth
needs.
With
the
development
of
advanced
proteomics
techniques,
hundreds
distinct
types
PTMs
have
been
observed
in
a
wide
range
from
bacteria,
archaea,
and
eukarya.
To
identify
roles
these
PTMs,
scientists
applied
various
approaches.
However,
high
dynamics,
low
stoichiometry,
crosstalk
between
make
it
almost
impossible
obtain
homogeneously
modified
for
characterization
site-specific
effect
individual
PTM
on
target
proteins.
solve
this
problem,
genetic
code
expansion
(GCE)
strategy
has
introduced
into
field
studies.
Instead
modifying
after
translation,
GCE
incorporates
amino
acids
during
thus
generating
site-specifically
at
positions.
In
review,
we
summarize
systems
orthogonal
translation
installation
PTMs.
MedComm,
Journal Year:
2022,
Volume and Issue:
3(4)
Published: Nov. 3, 2022
Abstract
Protein
phosphorylation
is
an
important
post‐transcriptional
modification
involving
extremely
wide
range
of
intracellular
signaling
transduction
pathways,
making
it
therapeutic
target
for
disease
intervention.
At
present,
numerous
drugs
targeting
protein
have
been
developed
the
treatment
various
diseases
including
malignant
tumors,
neurological
diseases,
infectious
and
immune
diseases.
In
this
review
article,
we
analyzed
303
small‐molecule
kinase
inhibitors
(PKIs)
registered
participated
in
clinical
research
obtained
a
database
named
Kinase
Inhibitor
Database
(PKIDB),
68
approved
by
Food
Drug
Administration
United
States.
Based
on
previous
classifications
kinases,
divided
these
human
kinases
into
eight
groups
nearly
50
families,
delineated
their
main
regulatory
upstream
downstream
targets.
These
include:
A,
G,
C
(AGC)
receptor
guanylate
cyclase
(RGC)
group,
calmodulin‐dependent
(CaMK)
CMGC
[Cyclin‐dependent
(CDKs),
Mitogen‐activated
(MAPKs),
Glycogen
synthase
(GSKs),
dc2‐like
(CLKs)]
sterile
(STE)‐MAPKs
tyrosine
(TK)
kinase‐like
(TKL)
atypical
other
groups.
Different
families
stimulate
or
inhibit
others,
forming
intricate
molecular
network.
This
takes
newly
new
PKIs
as
breakthrough
point,
aiming
to
clarify
network
relationship
each
pathway,
well
roles
intervention,
provide
direction
future
drug
development.
Aging and Disease,
Journal Year:
2024,
Volume and Issue:
unknown, P. 0 - 0
Published: Jan. 1, 2024
Alzheimer's
disease
(AD)
is
a
age-related
neurodegenerative
and
major
public
health
concern
both
in
Texas,
US
Worldwide.
This
mainly
characterized
by
amyloid-beta
(Aβ)
phosphorylated
Tau
(p-Tau)
accumulation
the
brains
of
patients
with
AD
increasing
evidence
suggests
that
these
are
key
biomarkers
AD.
Both
Aβ
p-tau
can
be
detected
through
various
imaging
techniques
(such
as
positron
emission
tomography,
PET)
cerebrospinal
fluid
(CSF)
analysis.
The
presence
individuals,
who
asymptomatic
or
have
mild
cognitive
impairment
indicate
an
increased
risk
developing
future.
Furthermore,
combination
often
used
for
more
accurate
diagnosis
prediction
progression.
Along
being
disease,
it
associated
other
chronic
conditions
such
cardiovascular
obesity,
depression,
diabetes
because
studies
shown
comorbid
make
people
vulnerable
to
In
first
part
this
review,
we
discuss
biofluid-based
Aβ,
p-Tau
&
plasma
could
alternative
sensitive
technique
diagnose
second
part,
underlying
molecular
mechanisms
linked
how
they
affect
clinical
care.
Physiological Reviews,
Journal Year:
2024,
Volume and Issue:
104(3), P. 931 - 982
Published: Feb. 1, 2024
Mass
spectrometry-based
proteomics
is
a
sophisticated
identification
tool
specializing
in
portraying
protein
dynamics
at
molecular
level.
Proteomics
provides
biologists
with
snapshot
of
context-dependent
and
proteoform
expression,
structural
conformations,
dynamic
turnover,
protein-protein
interactions.
Cardiac
can
offer
broader
deeper
understanding
the
mechanisms
that
underscore
cardiovascular
disease,
it
foundational
to
development
future
therapeutic
interventions.
This
review
encapsulates
evolution,
current
technologies,
perspectives
proteomic-based
mass
spectrometry
as
applies
study
heart.
Key
technological
advancements
have
allowed
researchers
proteomes
single-cell
level
employ
robot-assisted
automation
systems
for
enhanced
sample
preparation
techniques,
increase
fidelity
spectrometers
has
unambiguous
numerous
posttranslational
modifications.
Animal
models
ranging
from
early
animal
experiments
heart
failure
preserved
ejection
fraction,
provided
tools
challenging
organ
laboratory.
Further
will
pave
way
implementation
even
closer
within
clinical
setting,
allowing
not
only
scientists
but
also
patients
benefit
an
interplay
relates
cardiac
disease
physiology.
Cell & Bioscience,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Feb. 12, 2024
Abstract
Protein
post-translational
modifications
(PPTMs)
refer
to
a
series
of
chemical
that
occur
after
the
synthesis
protein.
Proteins
undergo
different
such
as
phosphorylation,
acetylation,
ubiquitination,
and
so
on.
These
can
alter
protein’s
structure,
function,
interaction,
thereby
regulating
its
biological
activity.
In
neurodegenerative
diseases,
several
proteins
abnormal
modifications,
which
leads
aggregation
deposition
protein,
thus
resulting
in
neuronal
death
related
diseases.
For
example,
main
pathological
features
Alzheimer’s
disease
are
beta-amyloid
protein
phosphorylation
tau
The
ubiquitination
loss
α-synuclein
onset
Parkinson’s
disease.
Other
diseases
Huntington’s
disease,
amyotrophic
lateral
sclerosis,
on
also
connected
with
PPTMs.
Therefore,
studying
PPTMs
is
critical
for
understanding
mechanism
these
development
significant
therapeutic
strategies.
This
work
reviews
implications
discusses
relevant
