bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 8, 2024
Abstract
The
ubiquitin
(Ub)
code
denotes
the
complex
Ub
architectures,
including
chains
of
different
length,
linkage-type
and
linkage
combinations,
which
enable
ubiquitination
to
control
a
wide
range
protein
fates.
Although
many
linkage-specific
interactors
have
been
described,
how
are
able
decode
more
architectures
is
not
fully
understood.
We
conducted
interactor
screen,
in
humans
yeast,
using
varying
as
well
as,
homotypic
heterotypic
branched
two
most
abundant
types
–
K48-
K63-linked
Ub.
identified
some
first
K48/K63
branch-specific
interactors,
histone
ADP-ribosyltransferase
PARP10/ARTD10,
E3
ligase
UBR4
huntingtin-interacting
HIP1.
Furthermore,
we
revealed
importance
chain
length
by
identifying
with
preference
for
Ub3
over
Ub2
chains,
Ub-directed
endoprotease
DDI2,
autophagy
receptor
CCDC50
p97-adaptor
FAF1.
Crucially,
compared
datasets
collected
common
DUB
inhibitors
Chloroacetamide
N-ethylmaleimide.
This
inhibitor-dependent
highlighting
inhibitor
consideration
during
pulldown
studies.
dataset
key
resource
understanding
read.
The Journal of Cell Biology,
Год журнала:
2024,
Номер
223(5)
Опубликована: Март 22, 2024
Ubiquitin
regulates
various
cellular
functions
by
posttranslationally
modifying
substrates
with
diverse
ubiquitin
codes.
Recent
discoveries
of
new
chain
topologies,
types
bonds,
and
non-protein
have
substantially
expanded
the
complexity
code.
Here,
we
describe
system
covering
basic
principles
recent
related
to
mechanisms,
technologies,
biological
importance.
Life Science Alliance,
Год журнала:
2024,
Номер
7(8), С. e202402740 - e202402740
Опубликована: Май 21, 2024
The
ubiquitin
(Ub)
code
denotes
the
complex
Ub
architectures,
including
chains
of
different
lengths,
linkage
types,
and
combinations,
which
enable
ubiquitination
to
control
a
wide
range
protein
fates.
Although
many
linkage-specific
interactors
have
been
described,
how
are
able
decode
more
architectures
is
not
fully
understood.
We
conducted
interactor
screen,
in
humans
yeast,
using
varying
as
well
homotypic
heterotypic
branched
two
most
abundant
types-lysine
48-linked
(K48)
lysine
63-linked
(K63)
Ub.
identified
some
first
K48/K63-linked
branch-specific
interactors,
histone
ADP-ribosyltransferase
PARP10/ARTD10,
E3
ligase
UBR4,
huntingtin-interacting
HIP1.
Furthermore,
we
revealed
importance
chain
length
by
identifying
with
preference
for
Ub3
over
Ub2
chains,
Ub-directed
endoprotease
DDI2,
autophagy
receptor
CCDC50,
p97
adaptor
FAF1.
Crucially,
compared
datasets
collected
common
deubiquitinase
inhibitors-chloroacetamide
N-ethylmaleimide.
This
inhibitor-dependent
highlighting
inhibitor
consideration
during
pulldown
studies.
dataset
key
resource
understanding
read.
The Journal of Biochemistry,
Год журнала:
2022,
Номер
171(4), С. 361 - 366
Опубликована: Янв. 10, 2022
Abstract
Protein
ubiquitylation
regulates
numerous
pathways,
and
the
diverse
information
encoded
by
various
forms
of
is
known
as
ubiquitin
code.
Recent
studies
revealed
that
branched
chains
are
abundant
in
mammalian
cells
regulate
important
pathways.
They
include
proteasomal
degradation
misfolded
disease-causing
proteins,
regulation
NF-κB
signalling
apoptotic
cell
fate
decisions.
Targeted
protein
through
chemical
degraders
emerged
a
transformative
therapeutic
paradigm
aimed
at
inducing
disappearance
unwanted
cellular
proteins.
To
further
improve
efficacy
target
expand
its
applications,
understanding
molecular
mechanism
degraders’
action
from
view
code
biology
required.
In
this
review,
I
discuss
roles
biological
pathways
chemically
induced
targeted
focusing
on
codes
we
have
characterized.
Frontiers in Molecular Biosciences,
Год журнала:
2023,
Номер
10
Опубликована: Фев. 8, 2023
Huntington’s
disease
(HD)
is
a
neurodegenerative
disorder
caused
by
CAG
repeat
expansion
in
the
N-terminus
of
HTT
gene.
The
translates
into
polyglutamine
mutant
(mHTT)
protein,
resulting
intracellular
aggregation
and
neurotoxicity.
Lowering
mHTT
protein
reducing
synthesis
or
improving
degradation
would
delay
prevent
onset
HD,
ubiquitin-proteasome
system
(UPS)
could
be
an
important
pathway
to
clear
proteins
prior
aggregation.
UPS
not
impaired
proteasomes
can
degrade
entirely
when
targeted
for
degradation.
However,
differently
ubiquitinated
compared
wild-type
(wtHTT),
suggesting
that
polyQ
affects
interaction
with
(de)
ubiquitinating
enzymes
subsequent
targeting
soluble
associated
several
ubiquitin-modifying
enzymes,
various
have
been
identified
are
linked
disease,
either
turnover
affecting
overall
homeostasis.
Here
we
describe
their
potential
mechanism
action
toward
improved
towards
proteostasis
machinery.
Cellular and Molecular Life Sciences,
Год журнала:
2024,
Номер
81(1)
Опубликована: Июль 30, 2024
Sepsis
is
a
life-threatening
organ
dysfunction
caused
by
dysregulated
host
response
to
infection.
The
inflammatory
cytokine
storm
causes
systemic
damage,
especially
acute
lung
injury
in
sepsis.
In
this
study,
we
found
that
the
expression
of
S-phase
kinase-associated
protein
2
(Skp2)
was
significantly
decreased
sepsis-induced
(ALI).
activated
MEK/ERK
pathway
and
inhibited
Skp2
pulmonary
epithelium,
resulting
reduction
K48
ubiquitination
solute
carrier
family
3
member
(SLC3A2),
thereby
impairing
its
membrane
localization
cystine/glutamate
exchange
function.
Consequently,
intracellular
redox
reactions
induced
ferroptosis
epithelial
cells,
leading
injury.
Finally,
demonstrated
intravenous
administration
mRNA-encapsulating
lipid
nanoparticles
(LNPs)
epithelium
alleviated
septic
mice.
Taken
together,
these
data
provide
an
innovative
understanding
underlying
mechanisms
ALI
promising
therapeutic
strategy
for
