bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Abstract
The
SUMO-targeted
E3
ubiquitin
ligase
RNF4
plays
an
important
role
in
safeguarding
genome
and
proteome
integrity.
recognizes
polySUMO
modified
proteins
induces
their
proteolytic
or
non-proteolytic
ubiquitylation.
Given
the
key
function
of
maintaining
stability,
we
explored
its
cancer
cell
survival
as
a
potential
drug
target.
We
found
that
is
overexpressed
acute
myeloid
leukemia
high
expression
levels
correlate
with
poor
patients.
Depletion
exerts
antiproliferative
effects
AML
cells
increased
sensitivity
towards
antileukemic
drugs
thus
validating
vulnerability
AML.
To
develop
PROTACs
for
targeted
degradation
RNF4,
aimed
to
exploit
recently
described
cysteine-reactive
ligand
CCW16,
synthesized
set
CCW16-derived
degrader
molecules
using
established
VHL-
CRBN-E3
ligands.
validated
covalent
binding
CCW16
cysteine
residues
outside
RING
domain
recombinant
protein.
However,
none
were
active
degrading
panel
different
lines.
Consistent
reactivity
chosen
electrophile,
detected
cellular
context
attachment
accessible
cysteines
large
number
including
linkage
catalytic
members
peroxiredoxin
family.
Furthermore,
exposure
induced
upregulation
heme
oxygenase
1,
ferroptosis
marker
impaired
viability
distinct,
RNF4-independent,
ferroptotic
death
pathway.
Molecular Cell,
Journal Year:
2024,
Volume and Issue:
84(23), P. 4629 - 4644.e9
Published: Nov. 14, 2024
Selenium-dependent
glutathione
peroxidase
4
(GPX4)
is
the
guardian
of
ferroptosis,
preventing
unrestrained
(phospho)lipid
peroxidation
by
reducing
phospholipid
hydroperoxides
(PLOOH).
However,
contribution
other
peroxidases
in
ferroptosis
protection
remains
unclear.
We
show
that
cells
lacking
GPX4
still
exhibit
substantial
PLOOH-reducing
capacity,
suggesting
a
alternative
PLOOH
peroxidases.
By
scrutinizing
potential
candidates,
we
found
although
overexpression
peroxiredoxin
6
(PRDX6),
thiol-specific
antioxidant
enzyme
with
reported
activity,
failed
to
prevent
its
genetic
loss
sensitizes
cancer
ferroptosis.
Mechanistically,
uncover
PRDX6,
beyond
known
acts
as
selenium-acceptor
protein,
facilitating
intracellular
selenium
utilization
and
efficient
incorporation
into
selenoproteins,
including
GPX4.
Its
physiological
significance
was
demonstrated
reduced
expression
Prdx6-deficient
mouse
brains
increased
sensitivity
PRDX6-deficient
tumor
xenografts
mice.
Our
study
highlights
PRDX6
critical
player
directing
cellular
dictating
sensitivity.
Antioxidants,
Journal Year:
2025,
Volume and Issue:
14(4), P. 379 - 379
Published: March 23, 2025
As
a
moonlighting
protein
with
multiple
enzymatic
activities,
peroxiredoxin
6
(PRDX6)
maintains
redox
homeostasis,
regulates
phospholipid
metabolism,
and
mediates
intra-
inter-cellular
signaling
transduction.
Its
expression
activity
can
be
regulated
by
diverse
stressors.
However,
the
roles
relevant
mechanisms
of
these
regulators
in
various
conditions
have
yet
to
comprehensively
reviewed.
In
this
study,
stressors
were
systematically
reviewed
both
vivo
vitro
classified
into
chemical,
physical,
biological
categories.
We
found
that
regulatory
effects
on
PRDX6
primarily
mediated
via
key
transcriptional
factors
(e.g.,
NRF2,
HIF-1α,
SP1,
NF-κB),
micro-RNAs,
receptor-
or
kinase-dependent
pathways.
Additionally,
certain
stressors,
including
reactive
oxygen
species,
pH
fluctuations,
post-translational
modifications,
induced
structure-based
functional
switches
enzyme.
further
altered
under
disease
conditions,
particular
focus
neuropsychiatric
disorders
cancers,
proposed
concept
PRDX6-related
(PRD),
which
refers
spectrum
diseases
associated
dysregulated
expression.
Finally,
we
an
exogenous
supplementation
provided
preventive
therapeutic
potentials
for
oxidative
stress-related
injuries
models.
Taken
together,
review
underscores
critical
role
as
cellular
orchestrator
response
highlighting
its
clinical
potential
monitoring
development
strategies.
Applied Biosciences,
Journal Year:
2025,
Volume and Issue:
4(2), P. 19 - 19
Published: April 1, 2025
The
role
of
oxidants
and
antioxidants
in
inflammatory
bowel
disease
(IBD)
has
been
actively
explored
since
the
early
1980s,
starting
with
respiratory
burst
neutrophils
ischemia
pathology.
Since
that
time,
enzymatic
components
contributing
to
pool
reactive
oxygen
species,
including
superoxide,
H2O2,
lipid
hydroperoxides,
counteracting
antioxidants—catalase,
glutathione
peroxidases
(Gpx),
peroxiredoxins
(PRDX),
superoxide
dismutases,
others—have
fleshed
out.
My
perspective
on
IBD
is
from
balance
or
imbalance
oxidant
sources
process.
I
will
present
evidence
involvement
antioxidant
processes
based,
as
much
possible,
my
experiences
Gpxs.
This
be
discussed
terms
both
immune
system
local
systems.
As
Gpxs
are
generally
selenium-dependent,
possible
deficiencies
selenium
uptake
active
impact
Gpx
expression
explored.
more
recently
introduced
ferroptosis,
an
iron-dependent
peroxidation-based
pathological
process,
reviewed
for
its
IBD.
The EMBO Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 20, 2025
Abstract
Oxygen
and
sulfur,
both
members
of
the
chalcogen
group
(group
16
elements),
play
fundamental
roles
in
life.
Ancient
organisms
primarily
utilized
sulfur
for
energy
metabolism,
while
rise
atmospheric
oxygen
facilitated
evolution
aerobic
organisms,
enabling
highly
efficient
production.
Nevertheless,
all
modern
aerobes
anaerobes,
must
protect
themselves
from
toxicity.
Interestingly,
still
rely
on
survival.
This
dependence
has
been
illuminated
by
recent
discovery
supersulfides,
a
novel
class
biomolecules,
made
possible
through
advancements
technology
analytical
methods.
These
breakthroughs
are
reshaping
our
understanding
biological
processes
emphasizing
intricate
interplay
between
regulating
essential
redox
reactions.
review
summarizes
latest
insights
into
oxygen,
their
interdependence
key
processes,
contributions
to
adaptive
responses
environmental
stressors.
By
exploring
these
interactions,
we
aim
provide
comprehensive
perspective
how
elements
drive
survival
strategies
across
diverse
life
forms,
highlighting
indispensable
human
health
sustenance
