Journal of Developmental Biology,
Год журнала:
2022,
Номер
10(3), С. 31 - 31
Опубликована: Июль 27, 2022
Protein
kinase
CK2
(CK2)
is
a
ubiquitous
holoenzyme
involved
in
wide
array
of
developmental
processes.
The
involvement
events
such
as
neurogenesis,
cardiogenesis,
skeletogenesis,
and
spermatogenesis
essential
for
the
viability
almost
all
organisms,
its
role
has
been
conserved
throughout
evolution.
Further
into
adulthood,
continues
to
function
key
regulator
pathways
affecting
crucial
processes
osteogenesis,
adipogenesis,
chondrogenesis,
neuron
differentiation,
immune
response.
Due
vast
multitude
pathways,
aberrant
functioning
this
leads
embryonic
lethality
numerous
diseases
disorders,
including
cancer
neurological
disorders.
As
result,
popular
target
interventions
aiming
treat
aforementioned
diseases.
Specifically,
two
inhibitors,
namely
CX-4945
CIBG-300,
are
early
stages
clinical
testing
exhibit
promise
treating
other
Further,
researchers
around
world
focusing
on
bone
This
review
summarizes
current
understanding
development,
structure
CK2,
targets
signaling
implication
disease
progression,
recent
therapeutics
developed
inhibit
dysregulation
various
Trends in Biochemical Sciences,
Год журнала:
2023,
Номер
48(5), С. 477 - 490
Опубликована: Фев. 6, 2023
Intrinsically
disordered
regions
(IDRs)
are
especially
enriched
among
proteins
that
regulate
chromatin
and
transcription.
As
a
result,
mechanisms
influence
specificity
of
IDR-driven
interactions
have
emerged
as
exciting
unresolved
issues
for
understanding
gene
regulation.
We
review
the
molecular
elements
frequently
found
within
IDRs
confer
regulatory
specificity.
In
particular,
we
summarize
differing
roles
low-complexity
(LCRs)
short
linear
motifs
(SLiMs)
towards
selective
nuclear
Examination
highlights
SLiMs
organizers
selectivity,
with
widespread
in
regulation
integration
cellular
signals.
Analysis
recurrent
between
folded
domains
suggests
diverse
avenues
to
phase-separated
condensates
opportunities
manipulate
these
control
biological
activity.
Cell Reports,
Год журнала:
2025,
Номер
unknown, С. 115109 - 115109
Опубликована: Янв. 1, 2025
Alzheimer's
disease
(AD)
diagnosis
relies
on
the
presence
of
extracellular
β-amyloid
(Aβ)
and
intracellular
hyperphosphorylated
tau
(p-tau).
Emerging
evidence
suggests
a
potential
link
between
AD
pathologies
infectious
agents,
with
herpes
simplex
virus
1
(HSV-1)
being
leading
candidate.
Our
investigation,
using
metagenomics,
mass
spectrometry,
western
blotting,
decrowding
expansion
pathology,
detects
HSV-1-associated
proteins
in
human
brain
samples.
Expression
herpesvirus
protein
ICP27
increases
severity
strongly
colocalizes
p-tau
but
not
Aβ.
Modeling
organoids
shows
that
HSV-1
infection
elevates
phosphorylation.
Notably,
reduces
expression
markedly
decreases
post-infection
neuronal
death
from
64%
to
7%.
This
modeling
prompts
investigation
into
cGAS-STING-TBK1
pathway
products,
nuclear
factor
(NF)-κB
IRF-3,
which
AD.
Furthermore,
experimental
activation
STING
enhances
phosphorylation,
while
TBK1
inhibition
prevents
it.
Together,
these
findings
suggest
phosphorylation
acts
as
an
innate
immune
response
AD,
driven
by
cGAS-STING.
Viruses,
Год журнала:
2022,
Номер
14(7), С. 1415 - 1415
Опубликована: Июнь 28, 2022
Molecular
mimicry
between
viral
antigens
and
host
proteins
can
produce
cross-reacting
antibodies
leading
to
autoimmunity.
The
coronavirus
SARS-CoV-2
causes
COVID-19,
a
disease
curiously
resulting
in
varied
symptoms
outcomes,
ranging
from
asymptomatic
fatal.
Autoimmunity
due
molecular
may
provide
an
explanation.
Thus,
we
computationally
investigated
Spike
known
epitopes.
We
discovered
hotspots
highlight
two
examples
with
tentative
high
autoimmune
potential
implications
for
understanding
COVID-19
complications.
show
that
TQLPP
motif
thrombopoietin
shares
similar
antibody
binding
properties.
Antibodies
induce
thrombocytopenia,
condition
observed
patients.
Another
motif,
ELDKY,
is
shared
multiple
human
proteins,
such
as
PRKG1
involved
platelet
activation
calcium
regulation,
tropomyosin,
which
linked
cardiac
disease.
tropomyosin
cause
complications
blood-clotting
disorders
disease,
respectively.
Our
findings
illuminate
pathogenesis
the
importance
of
considering
when
developing
therapeutic
interventions
reduce
adverse
reactions.
Frontiers in Oncology,
Год журнала:
2022,
Номер
12
Опубликована: Март 14, 2022
WNT/β-catenin
signaling
is
a
highly
complex
pathway
that
plays
diverse
roles
in
various
cellular
processes.
While
WNT
ligands
usually
signal
through
their
dedicated
Frizzled
receptors,
the
decision
to
β-catenin-dependent
or
-independent
manner
rests
upon
type
of
co-receptors
used.
Canonical
β-catenin-dependent,
whereas
non-canonical
β-catenin-independent
according
classical
definition.
This
still
holds
true,
albeit
with
some
added
complexity,
as
both
pathways
seem
cross-talk
intertwined
networks
involve
use
different
ligands,
and
co-receptors.
β-catenin
can
be
directly
phosphorylated
by
kinases
governing
its
participation
either
canonical
pathways.
Moreover,
co-activators
associate
determine
output
terms
induction
genes
promoting
proliferation
differentiation.
In
this
review,
we
provide
an
overview
how
protein
phosphorylation
controls
signaling,
particularly
human
cancer.
Journal of Chemical Information and Modeling,
Год журнала:
2022,
Номер
62(22), С. 5715 - 5728
Опубликована: Окт. 31, 2022
The
prediction
of
ligand
efficacy
has
long
been
linked
to
thermodynamic
properties
such
as
the
equilibrium
dissociation
constant,
which
considers
both
association
and
rates
a
defined
protein-ligand
complex.
In
last
15
years,
there
paradigm
shift,
with
an
increased
interest
in
determination
kinetic
drug-target
residence
time
since
they
better
correlate
compared
other
parameters.
this
article,
we
present
thermal
titration
molecular
dynamics
(TTMD),
alternative
computational
method
that
combines
series
simulations
performed
at
progressively
increasing
temperatures
scoring
function
based
on
interaction
fingerprints
for
qualitative
estimation
protein-ligand-binding
stability.
protocol
applied
four
different
pharmaceutically
relevant
test
cases,
including
protein
kinase
CK1δ,
CK2,
pyruvate
dehydrogenase
2,
SARS-CoV-2
main
protease,
variety
ligands
sizes,
structures,
experimentally
determined
affinity
values.
all
TTMD
was
successfully
able
distinguish
between
high-affinity
compounds
(low
nanomolar
range)
low-affinity
ones
(micromolar),
proving
be
useful
screening
tool
prioritization
drug
discovery
campaign.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(4), С. 2257 - 2281
Опубликована: Фев. 6, 2023
CK2
(casein
kinase
2)
is
a
serine/threonine
protein
that
ubiquitous
in
eukaryotic
cells
and
plays
important
roles
variety
of
cellular
functions,
including
cell
growth,
apoptosis,
circadian
rhythms,
DNA
damage
repair,
transcription,
translation.
involved
cancer
pathogenesis
the
occurrence
many
diseases.
Therefore,
targeting
promising
therapeutic
strategy.
Although
CK2-specific
small-molecule
inhibitors
have
been
developed,
only
CX-4945
has
progressed
to
clinical
trials.
In
recent
years,
novel
gradually
become
research
hotspot,
which
expected
overcome
limitations
traditional
inhibitors.
Herein,
we
summarize
structure,
biological
disease
relevance
emphatically
analyze
structure-activity
relationship
(SAR)
binding
modes
We
also
discuss
latest
progress
strategies,
providing
insights
into
new
drugs
for
practice.
Biology,
Год журнала:
2023,
Номер
12(5), С. 694 - 694
Опубликована: Май 9, 2023
Macrophages
are
a
type
of
immune
cell
distributed
throughout
all
tissues
an
organism.
Allograft
inflammatory
factor
1
(AIF1)
is
calcium-binding
protein
linked
to
the
activation
macrophages.
AIF1
key
intracellular
signaling
molecule
that
participates
in
phagocytosis,
membrane
ruffling
and
F-actin
polymerization.
Moreover,
it
has
several
type-specific
functions.
plays
important
roles
development
diseases:
kidney
disease,
rheumatoid
arthritis,
cancer,
cardiovascular
diseases,
metabolic
diseases
neurological
disorders,
transplants.
In
this
review,
we
present
comprehensive
review
known
structure,
functions
role
diseases.
