Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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RNF2 is recruited by WASH to ubiquitinate AMBRA1 leading to downregulation of autophagy.
[wiskott-aldrich syndrome]
WASH
(
Wiskott-
Aldrich
syndrome
protein
(
WASP
)
and
SCAR
homolog
)
was
identified
to
function
in
endosomal
sorting
via
Arp
2
/
3
activation
.
We
previously
demonstrated
that
WASH
is
a
new
interactor
of
BECN
1
and
present
in
the
BECN
1
-
PIK
3
C
3
complex
with
AMBRA
1
.
The
AMBRA
1
-
DDB
1
-
CUL
4
A
complex
is
an
E
3
ligase
for
K
63
-
linked
ubiquitination
of
BECN
1
,
which
is
required
for
starvation-induced
autophagy
.
WASH
suppresses
autophagy
by
inhibition
of
BECN
1
ubiquitination
.
However
,
how
AMBRA
1
is
regulated
during
autophagy
remains
elusive
.
Here
,
we
found
that
RNF
2
associates
with
AMBRA
1
to
act
as
an
E
3
ligase
to
ubiquitinate
AMBRA
1
via
K
48
linkage
.
RNF
2
mediates
ubiquitination
of
AMBRA
1
at
lysine
45
.
Notably
,
RNF
2
deficiency
enhances
autophagy
induction
.
Upon
autophagy
induction
,
RNF
2
potentiates
AMBRA
1
degradation
with
the
help
of
WASH
.
WASH
deficiency
impairs
the
association
of
RNF
2
with
AMBRA
1
to
impede
AMBRA
1
degradation
.
Our
findings
reveal
another
novel
layer
of
regulation
of
autophagy
through
WASH
recruitment
of
RNF
2
for
AMBRA
1
degradation
leading
to
downregulation
of
autophagy
.
