Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Phosphorylation of NBR1 by GSK3 modulates protein aggregation.
[inclusion body myositis]
The
autophagy
receptor
NBR
1
(
neighbor
of
BRCA
1
gene
1
)
binds
UB
/
ubiquitin
and
the
autophagosome-conjugated
MAP
1
LC
3
/
LC
3
(
microtubule-associated
protein
1
light
chain
3
)
proteins
,
thereby
ensuring
ubiquitinated
protein
degradation
.
Numerous
neurodegenerative
and
neuromuscular
diseases
are
associated
with
inappropriate
aggregation
of
ubiquitinated
proteins
and
GSK
3
(
glycogen
synthase
kinase
3
)
activity
is
involved
in
several
of
these
proteinopathies
.
Here
we
show
that
NBR
1
is
a
substrate
of
GSK
3
.
NBR
1
phosphorylation
by
GSK
3
at
Thr
586
prevents
the
aggregation
of
ubiquitinated
proteins
and
their
selective
autophagic
degradation
.
Indeed
,
NBR
1
phosphorylation
decreases
protein
aggregation
induced
by
puromycin
or
by
the
DES
/
desmin
N
342
D
mutant
found
in
desminopathy
patients
and
stabilizes
ubiquitinated
proteins
.
Importantly
,
decrease
of
protein
aggregates
is
due
to
an
inhibition
of
their
formation
and
not
to
their
autophagic
degradation
as
confirmed
by
data
on
Atg
7
knockout
mice
.
The
relevance
of
NBR
1
phosphorylation
in
human
pathology
was
investigated
.
Analysis
of
muscle
biopsies
of
sporadic
inclusion
body
myositis
(
sIBM
)
patients
revealed
a
strong
decrease
of
NBR
1
phosphorylation
in
muscles
of
sIBM
patients
that
directly
correlated
with
the
severity
of
protein
aggregation
.
We
propose
that
phosphorylation
of
NBR
1
by
GSK
3
modulates
the
formation
of
protein
aggregates
and
that
this
regulation
mechanism
is
defective
in
a
human
muscle
proteinopathy
.
