Cancer Cell,
Journal Year:
2019,
Volume and Issue:
35(5), P. 721 - 737.e9
Published: May 1, 2019
The
mitochondrial
caseinolytic
protease
P
(ClpP)
plays
a
central
role
in
protein
quality
control
by
degrading
misfolded
proteins.
Using
genetic
and
chemical
approaches,
we
showed
that
hyperactivation
of
the
selectively
kills
cancer
cells,
independently
p53
status,
selective
degradation
its
respiratory
chain
substrates
disrupts
structure
function,
while
it
does
not
affect
non-malignant
cells.
We
identified
imipridones
as
potent
activators
ClpP.
Through
biochemical
studies
crystallography,
show
bind
ClpP
non-covalently
induce
proteolysis
diverse
structural
changes.
Imipridones
are
presently
clinical
trials.
Our
findings
suggest
general
concept
inducing
cell
lethality
through
activation
proteolysis.
Cell Death and Differentiation,
Journal Year:
2018,
Volume and Issue:
25(3), P. 486 - 541
Published: Jan. 23, 2018
Over
the
past
decade,
Nomenclature
Committee
on
Cell
Death
(NCCD)
has
formulated
guidelines
for
definition
and
interpretation
of
cell
death
from
morphological,
biochemical,
functional
perspectives.
Since
field
continues
to
expand
novel
mechanisms
that
orchestrate
multiple
pathways
are
unveiled,
we
propose
an
updated
classification
subroutines
focusing
mechanistic
essential
(as
opposed
correlative
dispensable)
aspects
process.
As
provide
molecularly
oriented
definitions
terms
including
intrinsic
apoptosis,
extrinsic
mitochondrial
permeability
transition
(MPT)-driven
necrosis,
necroptosis,
ferroptosis,
pyroptosis,
parthanatos,
entotic
death,
NETotic
lysosome-dependent
autophagy-dependent
immunogenic
cellular
senescence,
mitotic
catastrophe,
discuss
utility
neologisms
refer
highly
specialized
instances
these
processes.
The
mission
NCCD
is
a
widely
accepted
nomenclature
in
support
continued
development
field.
Cell Death and Differentiation,
Journal Year:
2017,
Volume and Issue:
25(1), P. 65 - 80
Published: Nov. 17, 2017
The
BCL-2
family
of
proteins
controls
cell
death
primarily
by
direct
binding
interactions
that
regulate
mitochondrial
outer
membrane
permeabilization
(MOMP)
leading
to
the
irreversible
release
intermembrane
space
proteins,
subsequent
caspase
activation
and
apoptosis.
affinities
relative
abundance
dictate
predominate
between
anti-apoptotic
pro-apoptotic
MOMP.
We
highlight
core
mechanisms
regulation
MOMP
with
an
emphasis
on
how
govern
fate.
address
critical
importance
both
concentration
show
differences
in
either
can
greatly
change
outcome.
Further,
we
explain
using
full-length
(versus
truncated
versions
or
peptides)
parse
out
family.
Finally,
discuss
post-translational
modifications
differing
intracellular
localizations
alter
apoptosis
proteins.
Successful
therapeutic
intervention
human
disease
requires
understanding
factors
mediate
major
cells.
Science,
Journal Year:
2018,
Volume and Issue:
359(6378)
Published: Feb. 22, 2018
Mitochondrial
apoptosis
is
mediated
by
BAK
and
BAX,
two
proteins
that
induce
mitochondrial
outer
membrane
permeabilization,
leading
to
cytochrome
c
release
activation
of
apoptotic
caspases.
In
the
absence
active
caspases,
DNA
(mtDNA)
triggers
innate
immune
cGAS/STING
pathway,
causing
dying
cells
secrete
type
I
interferon.
How
cGAS
gains
access
mtDNA
remains
unclear.
We
used
live-cell
lattice
light-sheet
microscopy
examine
network
in
mouse
embryonic
fibroblasts.
found
after
BAK/BAX
loss,
broke
down
large
pores
appeared
membrane.
These
macropores
allowed
inner
herniate
into
cytosol,
carrying
with
it
matrix
components,
including
genome.
Apoptotic
caspases
did
not
prevent
herniation
but
dismantled
cell
suppress
mtDNA-induced
signaling.
Cell Death and Disease,
Journal Year:
2019,
Volume and Issue:
10(3)
Published: Feb. 21, 2019
Abstract
The
BCl-2
family
has
long
been
identified
for
its
role
in
apoptosis.
Following
the
initial
discovery
of
BCL-2
context
B-cell
lymphoma
1980s,
a
number
homologous
proteins
have
since
identified.
members
Bcl-2
are
designated
as
such
due
to
their
homology
(BH)
domains
and
involvement
apoptosis
regulation.
BH
facilitate
members’
interactions
with
each
other
can
indicate
pro-
or
anti-apoptotic
function.
Traditionally,
these
categorised
into
one
three
subfamilies;
anti-apoptotic,
BH3-only
(pro-apoptotic),
pore-forming
‘executioner’
(pro-apoptotic)
proteins.
Each
distinct
pattern
activation,
localisation
response
cell
death
survival
stimuli.
All
vary
across
stress
types,
developmental
stage,
this
cause
delineation
roles
members.
Added
complexity
is
presence
relatively
uncharacterised
isoforms
many
There
gap
our
knowledge
regarding
function
isoforms.
domain
status
not
always
predictive
indicative
protein
function,
several
important
sequences,
which
contribute
apoptotic
activity
While
therapeutic
strategies
targeting
constantly
under
development,
it
imperative
that
we
understand
molecules,
attempting
target.
This
review,
discusses
current
With
significant
improvements
potential
splicing
therapies,
begin
distinctions
family,
limited
just
mechanisms
control,
but
outside
