Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,
Год журнала:
2021,
Номер
1876(2), С. 188606 - 188606
Опубликована: Авг. 8, 2021
Sarcomas
represent
a
distinct
group
of
rare
malignant
tumors
with
high
heterogeneity.
Limited
options
clinical
efficacy
for
the
metastatic
or
local
advanced
sarcoma
existed
despite
standard
therapy.
Recently,
targeted
therapy
according
to
molecular
and
genetic
phenotype
individual
is
promising
option.
Among
these
drugs,
anti-angiogenesis
achieved
favorable
in
sarcomas.
Inhibitors
targeting
cyclin-dependent
kinase
4/6,
poly-ADP-ribose
polymerase,
insulin-like
growth
factor-1
receptor,
mTOR,
NTRK,
metabolisms,
epigenetic
drugs
are
under
evaluation
sarcomas
bearing
corresponding
signals.
Immunotherapy
represents
method
solid
tumors.
However,
most
immune
"cold"
tumors,
only
alveolar
soft
part
undifferentiated
pleomorphic
respond
checkpoint
inhibitors.
Cellular
therapies
TCR-engineered
T
cells,
chimeric
antigen
receptor
tumor
infiltrating
lymphocytes,
nature
killer
cells
transfer
show
therapeutic
potential.
Identifying
tumor-specific
antigens
exploring
modulation
factors
arguing
immunotherapies
current
challenges.
This
review
focuses
on
mechanisms,
advances,
potential
strategies
immune-based
Experimental & Molecular Medicine,
Год журнала:
2022,
Номер
54(2), С. 91 - 102
Опубликована: Фев. 1, 2022
Abstract
High
mobility
group
box
1
(HMGB1)
is
a
nonhistone
nuclear
protein
that
has
multiple
functions
according
to
its
subcellular
location.
In
the
nucleus,
HMGB1
DNA
chaperone
maintains
structure
and
function
of
chromosomes.
cytoplasm,
can
promote
autophagy
by
binding
BECN1
protein.
After
active
secretion
or
passive
release,
extracellular
usually
acts
as
damage-associated
molecular
pattern
(DAMP)
molecule,
regulating
inflammation
immune
responses
through
different
receptors
direct
uptake.
The
release
fine-tuned
variety
factors,
including
posttranslational
modification
(e.g.,
acetylation,
ADP-ribosylation,
phosphorylation,
methylation)
machinery
cell
death
apoptosis,
pyroptosis,
necroptosis,
alkaliptosis,
ferroptosis).
this
minireview,
we
introduce
basic
focus
on
regulatory
mechanism
release.
Understanding
these
topics
may
help
us
develop
new
HMGB1-targeted
drugs
for
various
conditions,
especially
inflammatory
diseases
tissue
damage.
Nature Structural & Molecular Biology,
Год журнала:
2022,
Номер
29(4), С. 329 - 338
Опубликована: Март 24, 2022
Abstract
Poly(ADP-ribose)
polymerase
1
(PARP1)
is
implicated
in
the
detection
and
processing
of
unligated
Okazaki
fragments
other
DNA
replication
intermediates,
highlighting
such
structures
as
potential
sources
genome
breakage
induced
by
PARP
inhibition.
Here,
we
show
that
PARP1
activity
greatly
elevated
chicken
human
S
phase
cells
which
FEN1
nuclease
genetically
deleted
highest
behind
forks.
inhibitor
reduces
integrity
nascent
strands
both
wild-type
during
replication,
does
so
−
/
to
an
even
greater
extent
can
be
detected
postreplicative
single-strand
nicks
or
gaps.
Collectively,
these
data
inhibitors
impede
maturation
implicate
strand
discontinuities
cytotoxicity
compounds.
Trends in Biochemical Sciences,
Год журнала:
2023,
Номер
49(1), С. 68 - 78
Опубликована: Ноя. 30, 2023
DNA
single-strand
breaks
(SSBs)
are
among
the
most
common
lesions
arising
in
human
cells,
with
tens
to
hundreds
of
thousands
each
cell,
day.
Cells
have
efficient
mechanisms
for
sensing
and
repair
these
ubiquitous
lesions,
but
failure
processes
rapidly
remove
SSBs
can
lead
a
variety
pathogenic
outcomes.
The
threat
posed
by
unrepaired
is
illustrated
existence
at
least
six
genetic
diseases
which
SSB
(SSBR)
defective,
all
characterised
neurodevelopmental
and/or
neurodegenerative
pathology.
Here,
I
review
current
understanding
how
arise
impact
on
critical
molecular
processes,
such
as
replication
gene
transcription,
their
links
disease.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Ноя. 18, 2021
PARP1
and
PARP2
produce
poly(ADP-ribose)
in
response
to
DNA
breaks.
HPF1
regulates
PARP1/2
catalytic
output,
most
notably
permitting
serine
modification
with
ADP-ribose.
However,
is
substantially
more
abundant
cells
than
HPF1,
challenging
whether
can
pervasively
modulate
PARP1.
Here,
we
show
biochemically
that
efficiently
output
at
sub-stoichiometric
ratios
matching
their
relative
cellular
abundances.
rapidly
associates/dissociates
from
multiple
molecules,
initiating
before
initiates
on
glutamate/aspartate,
accelerating
initiation
be
comparable
elongation
reactions
forming
poly(ADP-ribose).
This
"hit
run"
mechanism
ensures
contributions
during
do
not
persist
interfere
PAR
chain
elongation.
We
provide
structural
insights
into
HPF1/PARP1
assembled
a
break,
assess
impact
retention
DNA.
Our
data
support
the
prevalence
of
serine-ADP-ribose
efficiency
required
for
an
acute
damage
response.
Redox Biology,
Год журнала:
2022,
Номер
58, С. 102530 - 102530
Опубликована: Ноя. 15, 2022
Diabetic
retinopathy
(DR)
and
other
diabetic
vascular
complications
are
the
leading
cause
of
death
disability
in
patients
with
suboptimum
glycemic
control.
In
pathogenesis
diseases,
hyperglycemia-induced
oxidative
stress,
DNA
damage,
poly-ADP-ribose-polymerase
(PARP)
hyperactivation
play
important
roles
endothelial
cell
impairment.
Adipose
differentiation-related
protein
FBXW7
was
reported
to
regulate
PGC-1α
stability
mitochondrial
homeostasis.
Here,
we
investigated
role
mechanism
repairing
stress
injuries
under
hyperglycemic
conditions.
promoted
hampered
activity
homologous
recombination
non-homologues
end
joining
pathway
for
double-strand
breaks
an
initiating
factor
PARP
complications.
The
abundant
mobilization
damage
repair
mediated
by
suppressed
activation,
downregulation
expression
both
human
cells
rat
retinas.
This
provided
a
new
method
inhibition,
superior
inhibitors
treating
complication.
Furthermore,
rescued
downregulated
NAD+
levels
ameliorated
dysfunction,
thereby
reducing
superoxide
production
These
effects
reversed
injury
leakage
retina,
providing
potential
future
treatment
strategy.
PARP1
and
PARP2
detect
DNA
breaks,
which
activates
their
catalytic
production
of
poly(ADP-ribose)
that
recruits
repair
factors
contributes
to
PARP1/2
release
from
DNA.
PARP
inhibitors
(PARPi)
are
used
in
cancer
treatment
target
activity,
interfering
with
increasing
persistence
on
damage.
In
addition,
certain
PARPi
exert
allosteric
effects
increase
retention
However,
no
clinical
exhibit
this
behavior
toward
PARP1.
contrast,
we
show
an
effect
retains
breaks
a
manner
depends
communication
between
the
binding
regions.
Using
mutant
mimics
inhibitor
effect,
observed
increased
at
cellular
damage
sites.
The
AZD5305
also
exhibited
clear
reverse
PARP2.
Our
results
can
help
explain
toxicity
suggest
ways
improve
moving
forward.
Seminars in Oncology,
Год журнала:
2023,
Номер
51(1-2), С. 2 - 18
Опубликована: Сен. 6, 2023
Genome
integrity
is
under
constant
insult
from
endogenous
and
exogenous
sources.
In
order
to
cope,
eukaryotic
cells
have
evolved
an
elaborate
network
of
DNA
repair
that
can
deal
with
diverse
lesion
types
exhibits
considerable
functional
redundancy.
PARP1
a
major
sensor
breaks
established
putative
roles
in
number
pathways
within
the
network,
including
single-
double-strand
as
well
protection
replication
fork.
Importantly,
target
small-molecule
PARP
inhibitors
(PARPi),
which
are
employed
treatment
homologous
recombination
(HR)-deficient
tumors,
latter
particularly
susceptible
accumulation
damage
due
inability
efficiently
highly
toxic
breaks.
The
clinical
success
PARPi
has
fostered
extensive
research
into
biology,
shed
light
on
involvement
various
genomic
transactions.
A
goal
field
been
understand
relationship
between
catalytic
inhibition
trapping.
specific
consequences
trapping
stability
basis
for
cytotoxicity
remain
matter
debate.
Finally,
increasingly
recognized
its
capacity
elicit/modulate
anti-tumor
immunity.
potential
is,
however,
hindered
by
development
resistance.
Hence,
efforts
invested
identifying
factors
promote
resistance
or
sensitize
PARPi.
current
review
provides
summary
advances
our
understanding
mechanistic
nature,
molecular
inhibition,
mechanisms
give
rise
