Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 29, 2024
The
Suppressor
of
Cytokine
Signalling
(SOCS)
protein
family
play
a
critical
role
in
cytokine
signalling
and
regulation
the
JAK/STAT
pathway
with
functional
consequences
to
immune
response.
Members
this
are
implicated
multiple
different
cascades
that
drive
autoimmune
diseases
cancer,
through
their
binding
phosphotyrosine
modified
proteins
as
well
ubiquitination
activity
part
Cullin5
RING
E3
ligases.
Here
we
review
SOCS
members
CISH
SOCS1-SOCS7,
focus
on
complex
immunity.
interactome
network
is
discussed,
intricate
mechanisms
which
alter
manage
system
assessed.
We
offer
structural
insights
into
how
engage
interacting
partners
native
substrates
at
protein-protein
interaction
level.
describe
knowledge
has
enabled
drug
discovery
efforts
date
propose
strategies
for
therapeutic
intervention
using
small
molecules,
either
via
direct
inhibition
or
leveraging
ligase
targeted
degradation.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Ноя. 26, 2024
Colorectal
cancer
(CRC)
remains
one
of
the
most
prevalent
and
fatal
malignancies
worldwide,
consistently
ranking
among
top
three
in
terms
incidence
mortality.
Despite
notable
advancements
early
detection
therapeutic
interventions,
survival
outcomes
for
advanced-stage
CRC
are
still
dismal,
largely
due
to
issues
such
as
drug
resistance
metastasis.
Recent
research
has
increasingly
implicated
JAK-STAT
signaling
pathway
a
pivotal
contributor
pathogenesis.
This
evolutionarily
conserved
plays
key
role
transmitting
extracellular
signals
nucleus,
thereby
modulating
gene
expression
involved
numerous
fundamental
biological
processes.
In
CRC,
dysregulation
is
frequently
observed
strongly
associated
with
tumor
progression,
including
processes
cellular
proliferation,
apoptosis,
metastasis,
immune
evasion,
sustenance
stem
cells.
Given
its
integral
advancement,
gained
recognition
viable
target.
Extensive
evidence
from
preclinical
clinical
models
supports
efficacy
safety
targeting
components
pathway,
presenting
new
possibilities
patients
particularly
addressing
enhancing
treatment
outcomes.
review
offers
detailed
exploration
focusing
on
regulatory
mechanisms
CRC-related
malignancies.
Moreover,
it
examines
association
between
protein
expression,
features,
prognosis,
potential
management.
Skin Research and Technology,
Год журнала:
2024,
Номер
30(8)
Опубликована: Авг. 1, 2024
Abstract
Background
Psoriasis
is
a
chronic
inflammatory
skin
disease
that
can
cause
systemic
inflammation
in
various
organs.
Rutin
has
been
suggested
to
fight
psoriasis,
but
the
signaling
pathways
by
which
it
works
need
be
explored.
Materials
and
methods
HaCaT
cells
co‐stimulated
with
interleukin
(IL)‐17,
IL‐22,
tumor
necrosis
factor‐alpha
(TNF‐α),
IL‐1α,
oncostatin
M
(M5)
were
used
as
an
vitro
cell
model
of
psoriasis.
The
proliferation
viability
determined
5‐ethynyl‐2′‐deoxyuridine
counting
assays.
Relative
mRNA
levels
IL‐6,
TNF‐α,
chemokines
(CXCL1
CXCL2),
anti‐microbial
peptides
(S100A7
S100A8)
detected
reverse
transcriptase‐quantitative
PCR.
Release
IL‐6
TNF‐α
from
was
measured
enzyme‐linked
immunosorbent
assay.
Keratin1,
Keratin5,
p‐JAK2,
p‐STAT3
protein
estimated
western
blotting.
Molecular
docking
predicted
binding
sites
for
STAT3.
Results
treatment
undercut
M5‐urged
increase
boost
cells.
Moreover,
M5
stimulation
mediated
upregulation
CXCL1,
CXCL2,
S100A7,
S100A8
partially
reversed
after
treatment.
In
addition,
induced
downregulation
Keratin1
Keratin5
proteins
well
p‐JAK2
attenuated
response
treatment,
manifesting
inhibited
M5‐promoted
aberrant
differentiation
impaired
M5‐mediated
activation
JAK2/STAT3
discovered
residues
GLN326
ASP334
STAT3
might
bind
Rutin.
Conclusion
blocked
signaling,
thus
attenuating
psoriasis‐related
anomalous
keratinocytes.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 14, 2024
Type
I
diabetes
is
an
autoimmune
disease
mediated
by
T-cell
destruction
of
β
cells
in
pancreatic
islets.
Currently,
there
no
known
cure,
and
treatment
consists
daily
insulin
injections.
Genome-wide
association
studies
twin
have
indicated
a
strong
genetic
heritability
for
type
implicated
several
genes.
As
most
strongly
associated
variants
are
noncoding,
still
lack
identification
functional
and,
therefore,
likely
causal
variants.
Given
that
many
these
reside
enhancer
elements,
we
tested
121
CD4+
with
T1D.
We
found
four
to
be
through
massively
parallel
reporter
assays.
Three
the
weaken
activity,
while
fourth
strengthens
activity.
link
their
cognate
genes
using
3D
genome
architecture
or
eQTL
data
validate
them
CRISPR
editing.
Validated
target
include
CLEC16A
SOCS1.
While
been
previously
1
other
diseases,
show
enhancers
controlling
expression
harbor
These
variants,
may
act
as
diabetic
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 29, 2024
The
Suppressor
of
Cytokine
Signalling
(SOCS)
protein
family
play
a
critical
role
in
cytokine
signalling
and
regulation
the
JAK/STAT
pathway
with
functional
consequences
to
immune
response.
Members
this
are
implicated
multiple
different
cascades
that
drive
autoimmune
diseases
cancer,
through
their
binding
phosphotyrosine
modified
proteins
as
well
ubiquitination
activity
part
Cullin5
RING
E3
ligases.
Here
we
review
SOCS
members
CISH
SOCS1-SOCS7,
focus
on
complex
immunity.
interactome
network
is
discussed,
intricate
mechanisms
which
alter
manage
system
assessed.
We
offer
structural
insights
into
how
engage
interacting
partners
native
substrates
at
protein-protein
interaction
level.
describe
knowledge
has
enabled
drug
discovery
efforts
date
propose
strategies
for
therapeutic
intervention
using
small
molecules,
either
via
direct
inhibition
or
leveraging
ligase
targeted
degradation.
