Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(24), С. 16714 - 16720
Опубликована: Июнь 7, 2024
Histone
monoaminylation
(
Язык: Английский
Construction of an anaplastic thyroid cancer stratification signature to guide immune therapy selection and validation of the pivotal gene HLF through in vitro experiments
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 13, 2025
While
most
thyroid
cancer
patients
have
a
favorable
prognosis,
anaplastic
carcinoma
(ATC)
remains
particularly
aggressive
form
with
median
survival
time
of
just
five
months.
Conventional
therapies
offer
limited
benefits
for
this
type
cancer.
Our
study
aims
to
identify
ATC
who
might
bene
t
from
immunotherapy.
uses
multiple
algorithms
by
R4.2.0,
and
gene
expression
clinical
data
are
collected
TCGA,
GEO
local
cohort.
In
vitro
experiments,
such
as
western
blot
immunofluorescence
staining,
performed.
Using
set
genes
uniquely
expressed
across
various
types
cancer,
we
developed
machine-learning
model
distinguish
each
within
the
dataset
(GSE60542,
GSE76039,
GSE33630,
GSE53157,
GSE65144,
GSE29265,
GSE82208,
GSE27155,
GSE58545,
GSE54958,
GSE32662).
These
allowed
us
stratify
into
three
distinct
groups,
exhibiting
significantly
different
responses
anti-PD1
therapy
determined
consensus
clustering.
Through
weighted
co-expression
network
analysis
(WGCNA),
identified
12
differentially
closely
associated
immunotherapy
outcomes.
This
led
creation
refined
signature
predicting
ATC's
immune
responsiveness
therapy,
which
was
further
validated
using
cohorts
TCGA
nine
melanoma
trials.
Among
genes,
HLF
stood
out
due
its
strong
association
hallmarks.
revealed
that
impedes
progression
down-regulating
epithelial-to-mesenchymal
transition
(EMT)
pathway,
reducing
T
cell
exhaustion,
increasing
sensitivity
sorafenib,
demonstrated
through
our
in-vitro
experiments.
Язык: Английский
Phenethylaminylation: Preliminary In Vitro Evidence for the Covalent Transamidation of Psychedelic Phenethylamines to Glial Proteins using 3,5-Dimethoxy-4-(2-Propynyloxy)-Phenethylamine as a Model Compound
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 17, 2025
Abstract
Psychedelics
are
well
known
for
their
ability
to
produce
profoundly
altered
states
of
consciousness.
But,
more
importantly,
the
effects
psychedelics
can
influence
neurobehavioral
changes
that
last
after
these
acute
subjective
end.
This
phenomenon
is
currently
being
leveraged
in
development
psychedelic-assisted
psychotherapies
treatment
multiple
neuropsychiatric
disorders.
The
cellular
and
molecular
mechanisms
by
which
single
doses
able
mediate
long-term
cognitive
an
active
area
research.
We
hypothesize
contribute
long
term
state
covalently
modifying
proteins.
post-translational
modification
possible
through
transglutaminase-mediated
transamidation
amine
termini
glutamine
carboxamide
residues.
Here,
we
synthesize
utilize
a
propargylated
analogue
mescaline
–
classic
serotonergic
psychedelic
phenethylamine
found
cacti
species
identify
putative
protein
targets
modifications
use
click-chemistry
primary
human
astrocyte
cell
culture
model.
Our
preliminary
findings
indicate
diverse
array
glial
proteins
may
be
substrates
transglutaminase
2-mediated
monoaminylation
our
model
(“phenethylaminylation”).
Based
on
points,
speculatively
highlight
new
directions
study
this
noncanonical
activity.
Язык: Английский
Transglutaminase 2-mediated Histone Monoaminylation and Its Role in Cancer
Bioscience Reports,
Год журнала:
2024,
Номер
44(8)
Опубликована: Авг. 1, 2024
Abstract
Transglutaminase
2
(TGM2)
has
been
known
as
a
well-characterized
factor
regulating
the
progression
of
multiple
types
cancer,
due
to
its
multifunctional
activities
and
ubiquitous
signaling
pathways
it
is
involved
in.
As
member
transglutaminase
family,
TGM2
catalyzes
protein
post-translational
modifications
(PTMs),
including
monoaminylation,
amide
hydrolysis,
cross-linking,
etc.,
through
transamidation
variant
glutamine-containing
substrates.
Recent
discoveries
revealed
histone
an
important
category
substrates,
thus
identifying
monoaminylation
emerging
epigenetic
mark,
which
highly
enriched
in
cancer
cells
possesses
significant
regulatory
functions
gene
transcription.
In
this
review,
we
will
summarize
recent
advances
TGM2-mediated
well
role
discuss
key
research
methodologies
better
understand
unique
thereby
shedding
light
on
therapeutic
potential
druggable
target
treatment.
Язык: Английский
pH-Controlled Chemoselective Rapid Azo-Coupling Reaction (CRACR) Enables Global Profiling of Serotonylation Proteome in Cancer Cells
Journal of Proteome Research,
Год журнала:
2024,
Номер
23(10), С. 4457 - 4466
Опубликована: Авг. 29, 2024
Serotonylation
has
been
identified
as
a
novel
protein
posttranslational
modification
for
decades,
where
an
isopeptide
bond
is
formed
between
the
glutamine
residue
and
serotonin
through
transamination.
Transglutaminase
2
(also
known
TGM2
or
TGase2)
was
proven
to
act
main
"writer"
enzyme
this
PTM,
number
of
key
regulatory
proteins
(including
small
GTPases,
fibronectin,
fibrinogen,
transporter,
histone
H3)
have
characterized
substrates
serotonylation.
However,
due
lack
pan-specific
antibodies
serotonylated
glutamine,
precise
enrichment
proteomic
profiling
serotonylation
still
remain
challenging.
In
our
previous
research,
we
developed
aryldiazonium
probe
specifically
label
in
bioorthogonal
manner,
which
depended
on
pH-controlled
chemoselective
rapid
azo-coupling
reaction.
Here,
report
application
photoactive
aryldiazonium-biotin
global
proteome
cancer
cells.
Thus,
over
1,000
were
from
HCT
116
cells,
many
are
highly
related
carcinogenesis.
Moreover,
sites
these
determined,
attributed
successful
chemical
approach.
Overall,
findings
provided
new
insights
into
significant
association
cellular
development,
further
suggesting
that
target
TGM2-mediated
monoaminylation
may
serve
promising
strategy
therapeutics.
Язык: Английский
Hippocampal γCaMKII dopaminylation promotes synaptic-to-nuclear signaling and memory formation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 20, 2024
ABSTRACT
Protein
monoaminylation
is
a
class
of
posttranslational
modification
(PTM)
that
contributes
to
transcription,
physiology
and
behavior.
While
recent
analyses
have
focused
on
histones
as
critical
substrates
monoaminylation,
the
broader
repertoire
monoaminylated
proteins
in
brain
remains
unclear.
Here,
we
report
development/implementation
chemical
probe
for
bioorthogonal
labeling,
enrichment
proteomics-based
detection
dopaminylated
brain.
We
identified
1,557
–
many
synaptic
including
γCaMKII,
which
mediates
Ca
2+
-dependent
cellular
signaling
hippocampal-dependent
memory.
found
γCaMKII
dopaminylation
largely
synaptic-to-nuclear
signaling,
neuronal
gene
expression
intrinsic
excitability,
contextual
These
results
indicate
role
adaptive
plasticity,
may
suggest
roles
these
phenomena
pathologies
associated
with
altered
monoaminergic
signaling.
Язык: Английский