bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 7, 2024
Summary
ZBP1
is
an
interferon-induced
nucleic
acid
(NA)
sensor
that
senses
unusual
Z-form
NA
(Z-NA),
a
type
of
left-handed
acid.
More
than
that,
the
binding
with
Z-NA
promotes
cell
death
and
inflammation.
However,
mechanisms
dampen
activation
to
fine-tune
inflammatory
responses
are
unclear.
Here
we
characterize
short
isoform
(referred
as
ZBP1-S)
intrinsic
suppresser
signaling
mediated
by
full-length
ZBP1.
Compared
ZBP1,
ZBP1-S
protein
has
Zα
domains
but
no
RHIM
domains.
Mechanistically,
depresses
ZBP1-mediated
competitive
for
Cells
from
mice
(
Rip1
D
325
A/D
A
)
Cleavage-resistant
RIP1-induced
autoinflammatory
(CRIA)
syndrome
alive
sensitive
IFN-induced
ZBP1-depedent
death.
Intriguingly,
cells
go
spontaneously
when
was
deleted,
indicating
driven
ZPB1
under
check
ZBP1-S.
Thus,
our
findings
reveal
alternative
splicing
Zbp1
represents
autogenic
inhibition
regulating
indicate
uncoupling
could
be
effective
strategy
against
auto-inflammations.
Highlight
ZBP1-short
expressed
synchronously
counteracts
suppresses
in
Zα-domain
dependent
manner.
prevents
autoactivation
cells.
Science Immunology,
Год журнала:
2024,
Номер
9(97)
Опубликована: Июль 5, 2024
The
past
20
years
have
seen
the
definition
of
human
monogenic
disorders
and
their
autoimmune
phenocopies
underlying
either
defective
or
enhanced
type
I
interferon
(IFN)
activity.
These
delineate
impact
IFNs
in
natural
conditions
demonstrate
that
only
a
narrow
window
IFN
activity
is
beneficial.
Insufficient
predisposes
humans
to
life-threatening
viral
diseases
(albeit
unexpectedly
few)
with
central
role
immunity
respiratory
cerebral
infection.
Excessive
IFN,
perhaps
counterintuitively,
appears
underlie
greater
number
autoinflammatory
and/or
known
as
interferonopathies,
whose
study
has
revealed
multiple
molecular
programs
involved
induction
signaling.
observations
suggest
manipulation
within
physiological
range
may
be
clinically
relevant
for
prevention
treatment
inflammatory
diseases.
Immunological Reviews,
Год журнала:
2025,
Номер
329(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Z‐nucleic
acid
binding
protein
1
(ZBP1)
is
an
innate
immune
sensor
recognizing
nucleic
acids
in
Z‐conformation.
Upon
sensing,
ZBP1
triggers
activation,
inflammation,
and
programmed
cell
death
during
viral
infections,
mice
development,
inflammation‐associated
diseases.
The
Zα
domains
of
sense
promote
RIP‐homotypic
interaction
motif
(RHIM)‐dependent
signaling
complex
assembly
to
mount
inflammation.
studies
on
spurred
understanding
the
role
Z‐form
RNA
DNA
cellular
physiological
functions.
In
particular,
short
genomic
segments,
endogenous
retroviral
elements,
3′UTR
regions
are
likely
sources
Z‐RNAs
that
orchestrate
Recent
seminal
identify
intriguing
association
with
adenosine
deaminase
acting
RNA‐1
(ADAR1),
cyclic
GMP‐AMP
synthase
(cGAS)
regulating
aberrant
chronic
cancer.
Thus,
attractive
target
aid
development
specific
therapeutic
regimes
for
disease
biology.
Here,
we
discuss
Z‐RNA
activation
death,
Also,
how
coordinates
intracellular
perturbations
homeostasis,
formation
regulate
diseases
Trends in Cell Biology,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 1, 2024
Adenosine
deaminase
acting
on
RNA
1
(ADAR1)
converts
adenosine
to
inosine
in
double-stranded
(dsRNA)
molecules,
a
process
known
as
A-to-I
editing.
ADAR1
deficiency
humans
and
mice
results
profound
inflammatory
diseases
characterised
by
the
spontaneous
induction
of
innate
immunity.
In
cells
lacking
ADAR1,
unedited
RNAs
activate
sensors.
These
include
melanoma
differentiation-associated
gene
5
(MDA5)
that
induces
expression
cytokines,
particularly
type
I
interferons
(IFNs),
protein
kinase
R
(PKR),
oligoadenylate
synthase
(OAS),
Z-DNA/RNA
binding
(ZBP1).
Immunogenic
'defused'
may
transcripts
from
repetitive
elements
other
long
duplex
RNAs.
Here,
we
review
these
recent
fundamental
discoveries
discuss
implications
for
human
diseases.
Some
tumours
depend
escape
immune
surveillance,
opening
possibility
unleashing
anticancer
therapies
with
inhibitors.
Science Immunology,
Год журнала:
2025,
Номер
10(105)
Опубликована: Март 7, 2025
Photosensitivity
is
observed
in
numerous
autoimmune
diseases
and
drives
poor
quality
of
life
disease
flares.
Elevated
epidermal
type
I
interferon
(IFN)
production
primes
for
photosensitivity
enhanced
inflammation,
but
the
substrates
that
sustain
amplify
this
cycle
remain
undefined.
We
show
IFN-induced
Z-DNA
binding
protein
1
(ZBP1)
stabilizes
ultraviolet
(UV)
B–induced
cytosolic
derived
from
oxidized
mitochondrial
DNA.
ZBP1
up-regulated
epidermis
adult
pediatric
patients
with
photosensitivity.
In
patient-derived
samples,
lupus
keratinocytes
accumulate
extensive
after
UVB
exposure,
transfection
results
stronger
IFN
through
cyclic
guanosine
monophosphate–adenosine
monophosphate
synthase–stimulator
genes
(cGAS-STING)
activation
compared
more
conventional
B-DNA.
knockdown
abrogates
UVB-induced
responses,
whereas
overexpression
a
lupus-like
phenotype
spontaneous
accumulation
production.
Our
highlight
as
critical
mediators
inflammation
uncover
how
IFNs
prime
cutaneous
Chemical Society Reviews,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
This
review
provides
a
comprehensive
overview
of
the
use
bioluminescence
assays
in
advancing
our
understanding
and
studying
cell
death
modalities
autophagy.
