bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: March 3, 2023
Abstract
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
which
caused
the
disease
2019
(COVID-19)
pandemic,
remains
a
global
health
concern
despite
vaccines,
neutralizing
antibodies,
and
antiviral
drugs.
Emerging
mutations
can
reduce
effectiveness
of
these
treatments,
suggesting
that
targeting
host
cell
factors
may
be
valuable
alternative.
N
-myristoyltransferases
(NMT)
are
essential
enzymes
for
protein
-myristoylation,
affecting
stability,
interaction,
localization,
function
numerous
proteins.
We
demonstrate
selective
inhibition
NMT
decreases
SARS-CoV-2
infection
by
90%
in
human
lung
primary
nasal
epithelial
cells,
choroid
plexus-cortical
neuron
organoids.
does
not
affect
viral
entry,
replication
or
release,
but
impairs
maturation
incorporation
envelope
proteins
into
newly
assembled
virions,
leading
to
compromised
infectivity
released
virions.
The
triggers
Golgi-bypassing
pathway
progeny
virion
egress,
occurs
through
endoplasmic
reticulum
lysosomal
intermediates.
Proteoglycan Research,
Journal Year:
2025,
Volume and Issue:
3(1)
Published: Jan. 1, 2025
ABSTRACT
Alterations
in
glycoconjugate
profiles
are
thought
to
promote
changes
cell‐to‐cell
and
cell‐to‐intracellular
extracellular
scaffold
interactions
human
disease.
The
nearly
unlimited
number
of
“glycoforms”
that
may
exist
nature
difficult
study
due
glycosylation
modifications
being
associated
with
non‐genome
coded
posttranscription
post‐translation
processes.
Specific
products
generated
by
dependent
on
concentration
sub‐cellular
locations
glycan
synthesis
processing
enzymes.
An
indirect
“high‐throughput”
approach
is
characterize
enzymes
(hydrolases
transferases)
single
cell
sequencing
all
types
tissue
diseases.
We
previously
identified
TMEM230
as
an
endoplasmic
reticulum
(ER)
protein
regulates
NOTCH
glycoprotein
receptor
ligand
signaling
zebrafish
blood
vessel
formation
destructive
remodeling
capacities
diverse
including
fibroblast,
phagocytic
immune
system
cells
patients
cancer
or
granulomatous
systemic
vasculitis
autoimmune
disorder.
represents
a
paradigm
mediated
signal
transduction
supports
the
role
modifications.
ER
initiates
earliest
steps
synthesis,
sorting,
trafficking.
As
remodeling,
Notch
hallmarks
disorders,
we
investigated
whether
aberrant
expression
was
also
rheumatoid
arthritis
(RA).
In
this
current
study,
analysis
supported
downregulated
synovial
RA
while
were
predominantly
upregulated.
contrast,
upregulated
high‐grade
compared
low‐grade
gliomas
it
N‐linked
(GlcNAc),
glycosaminoglycan
expression.
Our
collective
results
support
glycan/glycoconjugate
aggressive
gliomas.
therefore
be
therapeutic
target
marker
for
clinical
treatment
induced
autoimmunity
disorders
cancer.
The Plant Cell,
Journal Year:
2024,
Volume and Issue:
36(9), P. 3036 - 3056
Published: April 24, 2024
Plants
continuously
remodel
and
degrade
their
organelles
due
to
damage
from
metabolic
activities
environmental
stressors,
as
well
an
integral
part
of
cell
differentiation
programs.
Whereas
certain
use
local
hydrolytic
enzymes
for
limited
remodeling,
most
the
pathways
that
control
partial
or
complete
dismantling
rely
on
vacuolar
degradation.
Specifically,
selective
autophagic
play
a
crucial
role
in
recognizing
sorting
plant
organelle
cargo
clearance,
especially
under
cellular
stress
conditions
induced
by
factors
like
heat,
drought,
damaging
light.
In
these
short
reviews,
we
discuss
mechanisms
degradation
chloroplasts,
mitochondria,
endoplasmic
reticulum,
Golgi,
peroxisomes,
with
emphasis
autophagy,
recently
discovered
autophagy
receptors
organelles,
crosstalk
other
catabolic
pathways.
The Journal of Cell Biology,
Journal Year:
2023,
Volume and Issue:
222(11)
Published: Sept. 27, 2023
With
a
limited
number
of
genes,
cells
achieve
remarkable
diversity.
This
is
to
large
extent
achieved
by
chemical
posttranslational
modifications
proteins.
Amongst
these
are
the
lipid
that
have
unique
ability
confer
hydrophobicity.
The
last
decade
has
revealed
proteins
extremely
frequent
and
affect
great
variety
cellular
pathways
physiological
processes.
particularly
true
for
S-acylation,
only
reversible
modification.
enzymes
involved
in
S-acylation
deacylation
starting
be
understood,
list
undergo
this
modification
ever-increasing.
We
will
describe
state
knowledge
on
regulate
from
their
structure
regulation,
how
influences
target
proteins,
finally
offer
perspective
alterations
balance
between
may
contribute
disease.
Molecular Biology of the Cell,
Journal Year:
2025,
Volume and Issue:
36(4)
Published: Feb. 19, 2025
Cytoplasmic
K63-linked
polyubiquitin
signals
have
well-established
roles
in
endocytosis
and
selective
autophagy.
However,
how
these
help
to
direct
different
cargos
intracellular
trafficking
routes
is
unclear.
Here
we
report
that,
when
the
K63-polyubiquitin
signal
blocked
by
expression
of
a
high-affinity
sensor
(named
Vx3),
many
proteins
originating
from
plasma
membrane
are
found
trapped
clusters
small
vesicles
that
colocalize
with
ATG9A,
transmembrane
protein
plays
an
essential
role
Importantly,
whereas
ATG9A
required
for
cluster
formation,
other
core
autophagy
machinery
as
well
cargo
receptors
not
required.
Although
sequestered
vesicular
ATG9-dependent
manner,
additional
needed
induce
LC3
conjugation.
Upon
removal
Vx3
block,
K63-polyubiquitylated
rapidly
delivered
lysosomes.
These
observations
suggest
unexpected
K63-polyubiquitin–modified
proteins.
Journal of Molecular Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 169035 - 169035
Published: Feb. 1, 2025
The
endoplasmic
reticulum
(ER)
is
a
major
site
of
cellular
protein
synthesis.
Degradation
overabundant,
misfolded,
aggregating
or
unwanted
proteins
required
to
maintain
proteostasis
and
avoid
the
deleterious
consequences
aberrant
accumulation,
at
organismal
level.
While
extensive
research
has
shown
an
important
role
for
proteasomally-mediated,
ER-associated
degradation
(ERAD)
in
maintaining
proteostasis,
it
becoming
clear
that
there
substantial
lysosomal
"client"
from
ER
lumen
membrane
(ER-to-lysosome
degradation,
ERLAD).
Here
we
provide
brief
overview
broad
categories
ERLAD
-
predominantly
ER-phagy
(ER
autophagy)
pathways
related
processes.
We
collate
client
known
date,
either
individual
species
proteins.
Where
known,
summarise
molecular
mechanisms
by
which
they
are
selected
setting
client(s)
correct
cell
tissue
function.
Finally,
highlight
questions
remain
open
this
area.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(6), P. 2412 - 2412
Published: March 7, 2025
Aging
is
often
a
choice
between
developing
cancer
or
autoimmune
disorders,
due
in
part
to
loss
of
self-tolerance
immunological
recognition
rogue-acting
tumor
cells.
Self-tolerance
and
cell
by
the
immune
system
are
processes
very
much
dependent
on
specific
signatures
glycans
glycosylated
factors
present
plasma
membrane
stromal
components
tissue.
Glycosylated
generated
nearly
innumerable
variations
nature,
allowing
for
immensely
diverse
role
these
aging
flexibility
necessary
cellular
interactions
tissue
functionality.
In
previous
studies,
we
showed
that
differential
expression
TMEM230,
an
endoplasmic
reticulum
(ER)
protein
was
associated
with
enzymes
regulating
glycan
synthesis
processing
glycosylation
rheumatoid
arthritis
synovial
using
single-cell
transcript
sequencing.
this
current
study,
characterize
genes
pathways
co-modulated
all
types
processing,
as
well
glycosylation.
Genes
biological
molecular
hallmarks
were
mitochondria-dependent
oxidative
phosphorylation
reactive
oxygen
species
synthesis,
ER-dependent
stress
unfolded
response,
DNA
repair
(UV
response
P53
signaling
pathways),
senescence,
glycolysis
apoptosis
regulation
through
PI3K-AKT-mTOR
have
been
shown
play
important
roles
neurodegeneration
(such
Parkinson’s
Alzheimer’s
disease).
We
propose
downregulation
TMEM230
RNASET2
may
represent
paradigm
study
age-dependent
disorders
their
glycosylation,
signaling.