Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Окт. 2, 2022
Abstract
Extrachromosomal
circular
DNA
(eccDNA),
ranging
in
size
from
tens
to
millions
of
base
pairs,
is
independent
conventional
chromosomes.
Recently,
eccDNAs
have
been
considered
an
unanticipated
major
source
somatic
rearrangements,
contributing
genomic
remodeling
through
chimeric
circularization
and
reintegration
into
the
linear
genome.
In
addition,
origin
eccDNA
be
associated
with
essential
chromatin-related
events,
including
formation
super-enhancers
repair
machineries.
Moreover,
our
understanding
properties
functions
has
continuously
greatly
expanded.
Emerging
investigations
demonstrate
that
serve
as
multifunctional
molecules
various
organisms
during
diversified
biological
processes,
such
epigenetic
remodeling,
telomere
trimming,
regulation
canonical
signaling
pathways.
Importantly,
its
special
distribution
potentiates
a
measurable
biomarker
many
diseases,
especially
cancers.
The
loss
homeostasis
facilitates
tumor
initiation,
malignant
progression,
heterogeneous
evolution
An
in-depth
provides
novel
insights
for
precision
cancer
treatment.
this
review,
we
summarized
discovery
history
eccDNA,
discussed
biogenesis,
characteristics,
eccDNA.
emphasized
role
pathogenesis
evolution.
Therapeutically,
potential
clinical
applications
target
aberrant
multiple
diseases.
c-Myc
is
a
transcription
factor
that
constitutively
and
aberrantly
expressed
in
over
70%
of
human
cancers.
Its
direct
inhibition
has
been
shown
to
trigger
rapid
tumor
regression
mice
with
only
mild
fully
reversible
side
effects,
suggesting
this
be
viable
therapeutic
strategy.
Here
we
reassess
the
challenges
directly
targeting
c-Myc,
evaluate
lessons
learned
from
current
inhibitors,
explore
how
future
strategies
such
as
miniaturisation
Omomyc
E-box
binding
could
facilitate
translation
inhibitors
into
clinic.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Сен. 6, 2023
Abstract
Undruggable
proteins
are
a
class
of
that
often
characterized
by
large,
complex
structures
or
functions
difficult
to
interfere
with
using
conventional
drug
design
strategies.
Targeting
such
undruggable
targets
has
been
considered
also
great
opportunity
for
treatment
human
diseases
and
attracted
substantial
efforts
in
the
field
medicine.
Therefore,
this
review,
we
focus
on
recent
development
discovery
targeting
“undruggable”
their
application
clinic.
To
make
review
well
organized,
discuss
strategies
proteins,
including
covalent
regulation,
allosteric
inhibition,
protein–protein/DNA
interaction
targeted
nucleic
acid-based
approach,
immunotherapy
others.
Frontiers in Oncology,
Год журнала:
2021,
Номер
10
Опубликована: Янв. 27, 2021
Dysregulated
expression
of
the
transcription
factor
MYCN
is
frequently
detected
in
nervous
system
tumors
such
as
childhood
neuroblastoma.
Here,
gene
amplification
a
single
oncogenic
driver
inducing
neoplastic
transformation
neural
crest-derived
cells.
This
abnormal
one
strongest
predictors
poor
prognosis.
It
present
at
diagnosis
and
never
acquired
during
later
tumorigenesis
non-amplified
suggests
that
increased
an
early
event
these
cancers
leading
to
peculiar
dysregulation
cells
results
embryonal
or
cancer
stem-like
qualities,
self-renewal,
apoptotic
resistance,
metabolic
flexibility.
Cell stem cell,
Год журнала:
2021,
Номер
29(2), С. 209 - 216.e4
Опубликована: Дек. 21, 2021
In
human
embryos,
the
initiation
of
transcription
(embryonic
genome
activation
[EGA])
occurs
by
eight-cell
stage,
but
its
exact
timing
and
profile
are
unclear.
To
address
this,
we
profiled
gene
expression
at
depth
in
metaphase
II
oocytes
bipronuclear
(2PN)
one-cell
embryos.
High-resolution
single-cell
RNA
sequencing
revealed
previously
inaccessible
oocyte-to-embryo
changes.
This
confirmed
transcript
depletion
following
fertilization
(maternal
degradation)
also
uncovered
low-magnitude
upregulation
hundreds
spliced
transcripts.
Gene
analysis
predicted
embryonic
processes
including
cell-cycle
progression
chromosome
maintenance
as
well
transcriptional
activators
that
included
cancer-associated
regulators.
Transcription
was
disrupted
abnormal
monopronuclear
(1PN)
tripronuclear
(3PN)
These
findings
indicate
initiates
sooner
than
thought.
The
pattern
promises
to
illuminate
involved
onset
development,
with
implications
for
epigenetic
inheritance,
stem-cell-derived
cancer.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Янв. 10, 2022
Abstract
Efforts
to
therapeutically
target
EZH2
have
generally
focused
on
inhibition
of
its
methyltransferase
activity,
although
it
remains
less
clear
whether
this
is
the
central
mechanism
whereby
promotes
cancer.
In
current
study,
we
show
that
directly
interacts
with
both
MYC
family
oncoproteins,
and
MYCN,
their
stabilization
in
a
methyltransferase-independent
manner.
By
competing
against
SCF
FBW7
ubiquitin
ligase
bind
counteracts
FBW7-mediated
MYC(N)
polyubiquitination
proteasomal
degradation.
Depletion,
but
not
enzymatic
inhibition,
induces
robust
degradation
inhibits
tumor
cell
growth
driven
neuroblastoma
small
lung
carcinoma.
Here,
demonstrate
proteins
as
global
oncogenic
effectors
pharmacologic
degraders
potential
targeted
cancer
therapeutics,
pointing
out
cancers
may
develop
inherent
resistance
canonical
inhibitors
currently
clinical
development.
Trends in Cell Biology,
Год журнала:
2022,
Номер
33(3), С. 235 - 246
Опубликована: Авг. 10, 2022
The
MYC
protooncogene
functions
as
a
universal
amplifier
of
transcription
through
interaction
with
numerous
factors
and
complexes
that
regulate
almost
every
cellular
process.
However,
comprehensive
model
explains
MYC's
actions
the
interplay
governing
complicated
dynamics
components
replication
machinery
is
still
lacking.
Here,
we
review
potency
an
oncogenic
driver
how
it
regulates
broad
spectrum
(effectors
regulators).
We
propose
'hand-over
model'
for
differential
partitioning
trafficking
unstructured
via
loose
network
between
various
gene-regulatory
factors.
Additionally,
article
discusses
unstructured-MYC
energetically
favors
efficient
modulation
energy
landscape
cycle.
