The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: March 21, 2025
Abstract
The
B
cell
lymphoma
2
(BCL2)
protein
family
critically
controls
apoptosis
by
regulating
the
release
of
cytochrome
c
from
mitochondria.
In
this
cutting-edge
review,
we
summarize
basic
biology
BCL2
including
canonical
and
non-canonical
functions,
highlight
milestones
research
to
clinical
applications
in
cancer
other
pathophysiological
conditions.
We
review
laboratory
development
BH3-mimetics
as
well
more
recent
approaches
proteolysis
targeting
chimeras
(PROTACs),
antibody-drug
conjugates
(ADCs)
tools
BH4
domain
BCL2.
first
BCL2-selective
BH3-mimetic,
venetoclax,
showed
remarkable
efficacy
with
manageable
toxicities
has
transformed
treatment
several
hematologic
malignancies.
Following
its
success,
chemically
similar
inhibitors
such
sonrotoclax
lisaftoclax
are
currently
under
evaluation,
alone
combination.
Genetic
analysis
highlights
importance
BCL-X
L
MCL1
across
different
types
possible
utility
these
proteins.
However,
or
been
challenging,
on-target
thrombocytopenia
for
cardiac
precluding
development.
Tumor-specific
inhibition
may
be
achieved
novel
using
PROTACs
selective
drug
delivery
strategies
would
transformational
many
subtypes
malignancy.
Taken
together,
envision
that
proteins,
while
already
a
success
story
translational
research,
foreseeable
future
have
broader
applicability
improve
multiple
diseases.
Language: Английский
ER Stress as a Sentinel Mechanism for ER Ca2+ Homeostasis
Tadashi Makio,
No information about this author
Junsheng Chen,
No information about this author
Thomas Simmen
No information about this author
et al.
Cell Calcium,
Journal Year:
2024,
Volume and Issue:
124, P. 102961 - 102961
Published: Oct. 18, 2024
Language: Английский
Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function
Cell Calcium,
Journal Year:
2025,
Volume and Issue:
126, P. 103000 - 103000
Published: Feb. 7, 2025
Language: Английский
Venom peptides regulating Ca2+ homeostasis: neuroprotective potential
Trends in Pharmacological Sciences,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
Language: Английский
Allosteric modulation of SERCA pumps in health and disease: structural dynamics, posttranslational modifications, and therapeutic potential
Journal of Molecular Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 169200 - 169200
Published: May 1, 2025
Sarco/endoplasmic
reticulum
(SR/ER)
Ca2+-ATPase
(SERCA)
pumps
are
ubiquitous
membrane
proteins
in
all
eukaryotic
cells,
playing
a
central
role
maintaining
intracellular
calcium
homeostasis
by
re-sequestering
Ca2+
ions
from
the
cytosol
into
SR/ER
at
expense
of
ATP
hydrolysis.
SERCA
well-characterized
components
transport
machinery
cell,
various
physiological
processes,
including
muscle
contraction,
energy
metabolism,
secretion
exocytosis,
gene
expression,
synaptic
transmission,
cell
survival,
and
fertilization.
Allosteric
regulation
plays
key
health
disease,
modulation
has
emerged
as
therapeutic
approach
for
treatment
cardiovascular,
muscular,
metabolic,
neurodegenerative
disorders.
In
this
review,
we
provide
comprehensive
overview
structural
dynamics
underlying
allosteric
SERCA,
focusing
on
effects
endogenous
regulatory
proteins,
ions,
ATP,
small-molecule
effectors
function
pump.
We
also
examine
detail
posttranslational
modifications
modulators
function,
oxidative
S-glutathionylation,
S-nitrosylation,
tyrosine
nitration,
carbonylation,
non-oxidative
that
include
SUMOylation,
acetylation,
O-GlcNAcylation,
phosphorylation,
ubiquitination.
Finally,
discuss
potential
challenges
pumps,
design
effectors,
microRNA-based
interventions,
targeted
strategies
modulate
regulation.
Overall,
review
aims
to
bridge
gap
between
mechanisms
translation
basic
science
discoveries
effective
therapies
targeting
pumps.
Language: Английский
Calcium channels as therapeutic targets in head and neck squamous cell carcinoma: current evidence and clinical trials
Jinye Lin,
No information about this author
Xijia Wang,
No information about this author
Shumei Ma
No information about this author
et al.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: Dec. 20, 2024
Head
and
neck
squamous
cell
carcinoma
(HNSCC)
originates
from
the
mucosal
epithelium
of
oral
cavity,
pharynx,
larynx,
is
marked
by
high
rates
recurrence
metastasis.
Calcium
signaling
associated
with
progression
HNSCC
development
drug
resistance.
Changes
in
calcium
ion
flow
can
trigger
severe
pathophysiological
processes,
including
malignant
transformation,
tumor
proliferation,
epithelial-mesenchymal
transition,
apoptosis
evasion.
channels
regulate
facilitate
these
processes.
Remodeling
has
become
one
most
prevalent
adaptive
mechanisms
cancer
cells.
Preclinical
clinical
evidence
indicates
that
alterations
are
crucial
for
HNSCC.
This
review
examines
role
evaluates
current
trials
targeting
to
assess
feasibility
signaling-based
therapies
Language: Английский