Cancer Discovery,
Journal Year:
2020,
Volume and Issue:
10(3), P. 351 - 370
Published: Feb. 18, 2020
Drugs
targeting
the
cell
cycle-regulatory
cyclin-dependent
kinase
(CDK)
4
and
6
have
been
approved
for
treatment
of
hormone
receptor-positive
breast
cancer,
inhibitors
other
cell-cycle
CDKs
are
currently
in
clinical
trials.
Another
class
CDKs,
transcription-associated
including
CDK7,
CDK8,
CDK9,
CDK12
CDK13,
critical
regulators
gene
expression.
Recent
evidence
suggests
several
novel
functions
these
regulation
epigenetic
modifications,
intronic
polyadenylation,
DNA-damage
responses,
genomic
stability.
Here,
we
summarize
our
current
understanding
transcriptional
their
utility
as
biomarkers,
potential
therapeutic
targets.
SIGNIFICANCE:
CDK
CDK4
CDK6
Several
studies
now
point
to
opportunities
by
inhibiting
well
vulnerabilities
with
PARP
immunotherapy
tumors
deficient
CDKs.
Science,
Journal Year:
2020,
Volume and Issue:
370(6520)
Published: Nov. 27, 2020
Dephosphorylating
RNA
polymerase
II
Transcription
in
metazoans
requires
coordination
of
multiple
factors
to
control
the
progression
polymerases
and
integrity
their
products.
Zheng
et
al.
identified
a
new
dual-enzyme
complex
called
INTAC,
which
is
composed
protein
phosphatase
2A
(PP2A)
core
enzyme
multisubunit
endonuclease
Integrator.
Structural
functional
studies
show
that
INTAC
functions
as
noncanonical
PP2A
holoenzyme
dephosphorylates
C-terminal
domain
attenuate
transcription.
This
study
provides
direct
connection
between
PP2A-mediated
dephosphorylation
transcriptional
regulation,
two
fundamental
cellular
processes.
Science
,
this
issue
p.
eabb5872
