Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
ERK involvement in resistance to apoptosis in keratinocytes with mutant keratin.
[epidermolysis bullosa simplex]
The
consequences
of
cell
stress
induced
by
misfolded
proteins
are
an
important
contributor
to
many
human
diseases
.
One
such
disease
is
epidermolysis
bullosa
simplex
(
EBS
)
,
caused
by
mutations
in
the
structural
proteins
(
keratins
K
5
or
K
14
)
of
the
proliferative
compartment
of
the
epidermis
(
basal
keratinocyte
layer
)
,
leading
to
cell
fragility
and
blistering
.
In
severe
EBS
,
the
mutation
is
associated
with
aggregates
of
nonfilamentous
keratin
protein
,
and
cell
lines
carrying
such
mutations
show
a
constitutively
activated
stress
response
.
Analysis
of
the
cellular
mechanisms
leading
to
cell
breakdown
on
physical
stress
may
point
the
way
to
mutation
-independent
therapeutic
approaches
to
these
incurable
genetic
disorders
.
We
therefore
subjected
EBS
cell
lines
,
immortalized
from
patients
with
EBS
,
to
an
oscillating
mechanical
stress
in
assays
designed
to
mimic
the
physical
trauma
that
leads
to
cell
breakdown
in
vivo
.
These
experiments
show
that
mechanical
stress
activates
extracellular
signal-regulated
kinase
(
ERK
)
signaling
in
these
cells
,
and
that
the
keratin
mutant
cells
also
show
a
resistance
to
apoptosis
following
mechanical
stress
that
is
reversed
by
inhibiting
ERK
.
The
consequences
of
constitutive
expression
of
large
amounts
of
defective
structural
protein
in
a
tissue
cell
must
be
properly
understood
for
the
development
of
safe
and
effective
therapies
for
these
disorders
.
Diseases
Validation
Diseases presenting
"blistering"
symptom
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
kindler syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom