In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target
Cell,
Год журнала:
2021,
Номер
184(21), С. 5357 - 5374.e22
Опубликована: Сен. 27, 2021
Язык: Английский
Prospects for pharmacological targeting of pseudokinases
Nature Reviews Drug Discovery,
Год журнала:
2019,
Номер
unknown
Опубликована: Март 8, 2019
Язык: Английский
Ubiquitin Ligase COP1 Suppresses Neuroinflammation by Degrading c/EBPβ in Microglia
Cell,
Год журнала:
2020,
Номер
182(5), С. 1156 - 1169.e12
Опубликована: Авг. 13, 2020
Язык: Английский
Tracing the origin and evolution of pseudokinases across the tree of life
Science Signaling,
Год журнала:
2019,
Номер
12(578)
Опубликована: Апрель 23, 2019
Pseudokinases
are
prevalent
across
species
and
contribute
diverse,
noncatalytic
signaling
functions.
Язык: Английский
Emerging concepts in pseudoenzyme classification, evolution, and signaling
Science Signaling,
Год журнала:
2019,
Номер
12(594)
Опубликована: Авг. 13, 2019
A
roadmap
for
identifying
and
analyzing
pseudoenzymes
is
proposed
this
rapidly
expanding
field.
Язык: Английский
There’s more to death than life: Noncatalytic functions in kinase and pseudokinase signaling
Journal of Biological Chemistry,
Год журнала:
2021,
Номер
296, С. 100705 - 100705
Опубликована: Янв. 1, 2021
Protein
kinases
are
present
in
all
domains
of
life
and
play
diverse
roles
cellular
signaling.
Whereas
the
impact
substrate
phosphorylation
by
protein
has
long
been
appreciated,
it
is
becoming
increasingly
clear
that
also
other,
noncatalytic,
functions.
Here,
we
review
recent
developments
understanding
noncatalytic
functions
kinases.
Many
activities
best
exemplified
devoid
enzymatic
activity
altogether—known
as
pseudokinases.
These
dead
proteins
illustrate
that,
beyond
conventional
notions
kinase
function,
catalytic
can
be
dispensable
for
biological
function.
Through
key
examples
mechanisms
activity:
allosteric
modulators;
protein-based
switches;
scaffolds
complex
assembly;
competitive
inhibitors
signaling
pathways.
In
common,
these
exploit
nature
fold
a
versatile
protein–protein
interaction
module.
intrinsically
linked
to
ability
switch
between
multiple
states,
function
shared
with
Finally,
consider
contemporary
landscape
small
molecules
modulate
kinases,
which,
although
challenging,
significant
potential
given
scope
health
disease.
quintessential
proteins.
Their
posttranslationally
modify
amino
acid
side
chains
phosphoryl
group
underlies
broad
swath
eukaryotic
biology
(1Hardman
G.
Perkins
S.
Brownridge
P.J.
Clarke
C.J.
Byrne
D.P.
Campbell
A.E.
Kalyuzhnyy
A.
Myall
Eyers
P.A.
Jones
A.R.
C.E.
Strong
anion
exchange-mediated
phosphoproteomics
reveals
extensive
human
non-canonical
phosphorylation.EMBO
J.
2019;
38e100847Crossref
PubMed
Scopus
(31)
Google
Scholar)
regulates
addition
catalyzing
transfer,
roles,
interacting
other
modifying
their
activity.
A
proportion
even
take
extreme—lacking
phosphoryl-transfer
completely—and
known
pseudokinases
(2Manning
Whyte
D.B.
Martinez
R.
Hunter
T.
Sudarsanam
The
complement
genome.Science.
2002;
298:
1912-1934Crossref
(5717)
Scholar,
3Zeqiraj
E.
van
Aalten
D.M.F.
Pseudokinases-remnants
evolution
or
regulators?.Curr.
Opin.
Struct.
Biol.
2010;
20:
772-781Crossref
(102)
4Eyers
Murphy
J.M.
Dawn
dead:
signal
new
adventures
cell
biology.Biochem.
Soc.
Trans.
2013;
41:
969-974Crossref
(60)
Scholar).
Originally
thought
evolutionary
remnants,
have
since
revealed
remarkably
pathways
(5Jacobsen
A.V.
secret
kinases:
Insights
into
non-catalytic
signalling
from
pseudokinases.Biochem.
2017;
45:
665-681Crossref
(41)
Importantly,
zombie
provide
window
often
unheralded,
nonenzymatic
performed
alive
enzyme
counterparts.
Catalytically
competent
diverse,
but
means
folds
similar
core
elements
show
little
variation
(Fig.
1A).
catalysis
bind
ATP,
coordinate
Mg2+,
catalyze
transfer.
generally
consist
of:
lysine
residue
within
VAIK
motif
N-terminal
lobe,
glycine
rich
loop
(Gly-loop),
which
features
enabling
ATP
binding;
an
aspartate
DFG-motif
activation
coordinates
magnesium
alongside
ATP;
HRD
contributed
C-terminal
acts
base
during
transfer
1B;
6Hanks
S.K.
Quinn
A.M.
family:
Conserved
deduced
phylogeny
domains.Science.
1988;
241:
42-52Crossref
Scholar)).
Any,
multiple,
lost
(7Kung
J.E.
Jura
N.
Prospects
pharmacological
targeting
pseudokinases.Nat.
Rev.
Drug
Discov.
18:
501-526Crossref
(28)
8Kwon
Scott
Taujale
Yeung
W.
Kochut
K.J.
Kannan
Tracing
origin
across
tree
life.Sci.
Signal.
12eaav3810Crossref
9Murphy
Zhang
Q.
Young
S.N.
Reese
M.L.
Bailey
F.P.
Ungureanu
D.
Hammarén
H.
Silvennoinen
O.
Varghese
L.N.
Chen
K.
Tripaydonis
Fukuda
Qin
et
al.A
robust
methodology
subclassify
based
on
nucleotide-binding
properties.Biochem.
2014;
457:
323-334Crossref
(0)
Depending
what
lost,
may
unable
nucleotides
(Class
I),
not
cations
II),
only
III),
both
cations,
still
carry
out
IV)
1C)
(9Murphy
Analyses
coding
genes
archaea,
bacteria,
eukaryotes
identified
pseudokinases,
(8Kwon
This
focuses
fold,
predicted
low
abundance
archaea
bacteria
(10Childers
W.S.
Shapiro
L.
pseudokinase
couples
enable
asymmetric
division
bacterium.Microb.
Cell.
2:
29-32Crossref
11Gee
C.L.
Papavinasasundaram
K.G.
Blair
S.R.
Baer
Falick
King
D.S.
Griffin
Venghatakrishnan
Zukauskas
Wei
J.-R.
Dhiman
R.K.
Crick
D.C.
Rubin
E.J.
Sassetti
C.M.
Alber
phosphorylated
controls
wall
synthesis
mycobacteria.Sci.
2012;
5ra7Crossref
Scholar),
our
more
broadly
prokaryotes
emerging
(12Kannan
Taylor
S.S.
Zhai
Y.
Venter
J.C.
Manning
Structural
functional
diversity
microbial
kinome.PLoS
2007;
5e17Crossref
(195)
13Pérez
Castañeda-García
Jenke-Kodama
Müller
Muñoz-Dorado
Eukaryotic-like
myxobacterial
kinome.Proc.
Natl.
Acad.
Sci.
U.
2008;
105:
15950-15955Crossref
(83)
proteome
contain
approximately
550
10%
retained
vertebrates,
∼10%
kinomes
designated
14Caenepeel
Charydczak
mouse
kinome:
Discovery
comparative
genomics
kinases.Proc.
2004;
101:
11707-11712Crossref
(237)
More
broadly,
some
species
expanded
complements.
For
instance,
plants
frequently
comprise
up
∼17%
half
kinase-like
selected
protists
(Toxoplasma
gondii
Giardia
lamblia)
lack
essential
residues
Such
expansion
concentrated
specific
classes
example,
undergone
massive
likely
due
important
role
innate
immunity
(15Jubic
L.M.
Saile
Furzer
O.J.
El
Kasmi
F.
Dangl
J.L.
Help
wanted:
Helper
NLRs
plant
immune
responses.Curr.
Plant
50:
82-94Crossref
(53)
scale
current
analyses
most
classification
sequence-based
rather
than
experimentally
verified.
While
computational
approaches
enlightening,
several
pertinent
demonstrate
need
couple
experimental
characterization.
seemingly
degraded
sequences
nonetheless
retain
phosphorylate
biomolecules
(16Beraki
Hu
X.
Broncel
M.
O'Shaughnessy
W.J.
Borek
Treeck
Divergent
membrane
ultrastructure
Toxoplasma
parasitophorous
vacuole.Proc.
116:
6361-6370Crossref
17Zhu
Venzke
Walimbe
A.S.
Anderson
M.E.
Fu
Kinch
Wang
Grishin
N.V.
Huang
Yu
Dixon
K.P.
Xiao
Structure
O-mannose
unique
active
site
architecture.Elife.
2016;
5e22238Crossref
(19)
18Yoshida-Moriguchi
Willer
Muntoni
Lee
Nelson
S.F.
SGK196
glycosylation-specific
required
dystroglycan
function.Science.
341:
896-899Crossref
(139)
19Lopez
V.A.
Park
B.C.
Nowak
Sreelatha
Zembek
P.
Fernandez
Servage
K.A.
Gradowski
Hennig
Tomchick
D.R.
Pawłowski
Krzymowska
Tagliabracci
V.S.
bacterial
effector
mimics
host
HSP90
client
undermine
immunity.Cell.
179:
205-218.e21Abstract
Full
Text
PDF
completely
unanticipated
distinct
(20Black
M.H.
Osinski
Bacterial
catalyzes
polyglutamylation
inhibit
SidE-family
ubiquitin
ligases.Science.
364:
787-792Crossref
21Sulpizio
Minelli
Wan
Burrowes
P.D.
Wu
Sanford
Shin
J.-H.
Williams
Goldberg
Smolka
M.B.
Mao
catalyzed
calmodulin-dependent
SidJ.Elife.
8e51162Crossref
22Bhogaraju
Bonn
Mukherjee
Adams
Pfleiderer
M.M.
Galej
W.P.
Matkovic
V.
Lopez-Mosqueda
Kalayil
Dikic
I.
Inhibition
ligases
SidJ-calmodulin
catalysed
glutamylation.Nature.
572:
382-386Crossref
(34)
23Sreelatha
Yee
Lopez
Pilch
Jiou
Karasiewicz-Urbańska
Łobocka
Orth
Kucharczyk
al.Protein
AMPylation
evolutionarily
conserved
pseudokinase.Cell.
2018;
175:
809-821.e19Abstract
(54)
Nonetheless,
coupled
bioinformatic
will
continued
insight
played
throughout
evolution.
Pseudokinases
led
realization
catalytically
inactive
enzymes
(pseudoenzymes)
almost
facets
(24Ribeiro
A.J.M.
Das
Dawson
Zaru
Orchard
Thornton
Orengo
C.
Zeqiraj
Emerging
concepts
pseudoenzyme
classification,
evolution,
signaling.Sci.
12eaat9797Crossref
(32)
Across
families
kingdoms
life,
regulate
processes
through
number
different
25Murphy
Mace
Live
let
die:
structure.Curr.
47:
95-104Crossref
26Murphy
Farhan
Bio-zombie:
rise
pseudoenzymes
537-544Crossref
(47)
Pseudoenzymes
include
pseudo-phosphatases,
pseudoproteases,
pseudoGTPases,
among
others.
Broadly
speaking,
as:
activators,
inhibitors,
assembly
complexes,
switches
2;
(25Murphy
Examples
each
categories
regulatory
surfaces
evolved
repurposed
toward
alternative
versions
same
eschewed
evolve
Thus,
while
this
does
mean
they
nonfunctional.
It
note
pseudogenes.
Pseudogenes
refer
incomplete
DNA
lacking
elements,
whereas
translated
encoded
genes.
focus
illustrative
at
molecular
level.
Because
definition
many
clearest
regulation
pseudoenzymes.
Noncatalytic
particularly
switches,
because
architecture
domain
encodes
on-
off-states.
conformations
though
elements.
activity,
simultaneously
scaffolds,
activators.
when
freed
constraints
retaining
elaborate
develop
novel
enzymes.
Accordingly,
offer
exemplars
additional,
unrecognized
might
conventional,
enzymes—in
keeping
idea
least
case
enzymes,
there
death
life.
One
best-characterized
modulation
cognate
either
promoting
attenuating
binding
partners.
arisen
gene
duplication
events,
pathway
partners
owing
common
expression
patterns
subcellular
localization,
noted
previously
(26Murphy
27Adrain
Freeman
New
lives
old:
Evolution
illustrated
iRhoms.Nat.
Mol.
Cell
13:
489-498Crossref
28Pils
B.
Schultz
Inactive
enzyme-homologues
find
processes.J.
340:
399-404Crossref
(109)
duplications
bring
enormous
liberty;
redundancy
arises
duplication,
no
necessity
maintain
geometry
mediate
striking
Janus
Kinase
(JAK)
family,
where
(termed
JH2)
occurs
tandem,
tyrosine
JH1)
attenuates
its
trans
receptor-scaffolded
dimers
(29Brooks
A.J.
Dai
O'Mara
Abankwa
Chhabra
Pelekanos
R.A.
Gardon
Tunny
Blucher
K.M.
Morton
Parker
M.W.
Sierecki
Gambin
Gomez
G.A.
Alexandrov
al.Mechanism
JAK2
growth
hormone
receptor.Science.
344:
1249783Crossref
(231)
30Varghese
Liau
N.P.D.
Laktyushin
Lucet
I.S.
Nicola
N.A.
Babon
J.J.
Mechanistic
insights
SOCS3-mediated
inhibition
myeloproliferative
neoplasm-associated
mutants
biochemical
structural
analyses.Biochem.
458:
395-405Crossref
31Babon
activation.Biochem.
462:
1-13Crossref
(143)
mechanism
debated
(31Babon
was
clearly
discovery
activating
mutations
(32James
Ugo
Le
Couédic
J.-P.
Staerk
Delhommeau
Lacout
Garçon
Raslova
Berger
Bennaceur-Griscelli
Villeval
Constantinescu
Casadevall
Vainchenker
clonal
mutation
leading
constitutive
causes
polycythaemia
vera.Nature.
2005;
434:
1144-1148Crossref
(2692)
promote
induce
hematopoietic
malignancies.
ancestors,
pseudoactive
sites
do
nucleotide,
diminish
loops,
adopt
discordant
Any
modifications
allosterically.
Via
intermolecular
interactions,
able
position
element,
αC
helix
N-lobe
partner
kinase.
Several
modes
dimerization
reported
influence
helix,
illuminated
detailed
studies,
highlight
versatility
3;
(33Lavoie
Li
Thevakumaran
Therrien
Sicheri
Dimerization-induced
allostery
regulation.Trends
Biochem.
39:
475-486Abstract
34Oliver
M.R.
Horne
C.R.
Shrestha
Keown
J.R.
Liang
L.-Y.
Sandow
Webb
A.I.
Goldstone
Metcalf
Granulovirus
PK-1
relies
side-to-side
mode
centered
helix.Nat.
Commun.
2021;
12:
1002Crossref
(1)
35Horne
whom
bell
tolls:
structure
kinase,
IRAK3.Structure.
29:
197-199Abstract
domain,
including:
back-to-back
(as
observed
Ire1
RNase
L
homodimers
(36Lee
K.P.K.
Dey
Neculai
Cao
Dever
T.E.
dual
basis
nonconventional
RNA
splicing.Cell.
132:
89-100Abstract
(238)
37Huang
Dong
Jha
B.K.
Duffy
N.M.
Orlicky
Talukdar
Pillon
M.C.
Ceccarelli
D.F.
L.C.K.
Juang
Y.-C.
D.Y.L.
Gaughan
Brinton
M.A.
al.Dimeric
bound
2-5A
interferon-induced
antiviral
activity.Mol.
53:
221-234Abstract
head-to-tail
EGFR
family
proteins,
such
HER3
pseudokinase:EGFR
(38Littlefield
Liu
Mysore
Shan
Shaw
D.E.
analysis
EGFR/HER3
heterodimer
mutations.Sci.
7ra114Crossref
Scholar)),
head-to-head
found
IRAK3
proposed
pseudokinase:IRAK4
pairs
(39Lange
S.M.
Nelen
M.I.
Cohen
Kulathu
Dimeric
suggests
negative
regulation.Structure.
238-251.e4Abstract
antiparallel
(exemplified
RAF:RAF
KSR
pseudokinase:RAF
heterodimers
(40Hu
Stites
E.C.
Germino
E.A.
Meharena
H.S.
Stork
P.J.S.
Kornev
A.P.
Allosteric
functionally
RAF
dimers.Cell.
154:
1036-1046Abstract
(162)
41Hatzivassiliou
Song
Yen
Brandhuber
B.J.
D.J.
Alvarado
Ludlam
M.J.C.
Stokoe
Gloor
S.L.
Vigers
Morales
Aliagas
Sideris
Hoeflich
al.RAF
prime
wild-type
activate
MAPK
enhance
growth.Nature.
464:
431-435Crossref
(1177)
42Rajakulendran
Sahmi
Lefrançois
dimerization-dependent
drives
activation.Nature.
2009;
461:
542-545Crossref
Scholar))
modes.
studies
raise
possibility
exert
those
exerted
recently
parallel
homodimerization
granuloviral
(34Oliver
yet
pseudokinase:kinase
pairs,
occupying
synonymous
Furthermore,
currently
poorly
understood,
allosterically
nonkinase
VRK3
to,
of,
VHR
phosphatase
(43Scheeff
E.D.
Eswaran
Bunkóczi
Knapp
site,
highly
putative
site.Structure.
17:
128-138Abstract
(127)
44Kang
T.-H.
Kim
K.-T.
Negative
ERK
VRK3-mediated
phosphatase.Nat.
2006;
8:
863-869Crossref
(64)
Overall,
findings
breadth
mediated
suggest
underappreciated
generally.
Deducing
precise
remains
major
challenge.
rely
elegant
chemical
knockin
approaches,
deletion
knockdown,
reveal
Over
past
30
years,
crystal
structures
captured
N-
C-lobes
loop,
pillars
hydrophobic
networks
spines)
continuum
conformations,
illustrating
intrinsic
dynamicity
(45Kornev
Dynamics-driven
kinases.Trends
2015;
40:
628-647Abstract
(136)
46Taylor
dynamic
proteins.Trends
2011;
36:
65-77Abstract
(517)
47Modi
Dunbrack
Jr.,
R.L.
Defining
nomenclature
6818-6827Crossref
flexibility
associated
Basally,
apoenzyme
exist
uncommitted
state
until
binding,
galvanizes
protein's
internal
poises
catalysis.
effectors
oligomerization
adoption
conformation
signified
intact
(R)-spine
Glu
engaged
salt
bridge
β3-strand
Lys
However,
if,
range
accessible
reflect
propensity
serve
switches?
Recent
via
interactions.
Consequently,
attractive
hypothesis
interactions
could
governed
pseudokinase,
additionally,
regulated
posttranslational
modifications.
concept
being
employed
Mixed
Lineage
domain-Like
(MLKL)
pseudokinase.
Unlike
solely
thus
interpretation
conformational
effects
confounded
additional
MLKL
terminal
necroptosis
pathway,
lytic
modality
unlike
cousin
apoptosis,
proteolytic
Caspases
(reviewed
(48Samson
A.L.
Garnish
S.E.
Hildebrand
Location,
location,
location:
compartmentalized
view
TNF-induced
necroptotic
14eabc6178Crossref
(3)
Instead,
following
insult,
inflammatory
receptor
pathogen
sensors,
leads
receptor-interacting
kinase-3
(RIPK3)
autophosphorylation
(49Meng
Czabotar
P.E.
post-translational
modifications.Cell
Death
Differ.
28:
861-883Crossref
(2)
Activated
RIPK3
then
substrate,
MLKL,
ac
Язык: Английский
Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells
Science Signaling,
Год журнала:
2018,
Номер
11(549)
Опубликована: Сен. 25, 2018
Covalent
EGFR
family
inhibitors
bind
to
and
induce
the
degradation
of
pseudokinase
TRIB2
kill
cancer
cells.
Язык: Английский
Cataloguing the dead: breathing new life into pseudokinase research
FEBS Journal,
Год журнала:
2020,
Номер
287(19), С. 4150 - 4169
Опубликована: Фев. 13, 2020
Pseudoenzymes
are
present
within
many,
but
not
all,
known
enzyme
families
and
lack
one
or
more
conserved
canonical
amino
acids
that
help
define
their
catalytically
active
counterparts.
Recent
findings
in
the
pseudokinase
field
confirm
evolutionary
repurposing
of
structurally
defined
bilobal
protein
kinase
fold
permits
distinct
biological
functions
to
emerge,
many
which
rely
on
conformational
switching,
as
opposed
catalysis.
In
this
analysis,
we
evaluate
progress
evaluating
several
members
‘dark’
pseudokinome
pertinent
drive
expanding
field.
Initially,
discuss
how
adaptions
erythropoietin‐producing
hepatocellular
carcinoma
(Eph)
receptor
tyrosine
domains
resulted
two
vertebrate
pseudokinases,
EphA10
EphB6,
co‐evolving
sequences
generate
new
motifs
likely
be
important
for
both
nucleotide
binding
catalysis‐independent
signalling.
Secondly,
conformationally
flexible
Tribbles
have
radiated
complex
vertebrates,
control
fundamental
aspects
cell
signalling
may
targetable
with
covalent
small
molecules.
Finally,
show
species‐level
duplicated
serine
histone
(PSKH)1
sequence
led
appearance
PSKH2,
whose
physiological
role
remains
mysterious.
conclusion,
patterns
discover
selectively
specific
when
they
modelled
alongside
closely
related
kinases,
found
located
functionally
regions
fold.
Interrogation
these
will
useful
future
evaluation
these,
other,
unstudied
human
kinome.
Язык: Английский
Pseudokinases: a tribble‐edged sword
FEBS Journal,
Год журнала:
2019,
Номер
287(19), С. 4170 - 4182
Опубликована: Окт. 17, 2019
Advances
in
the
understanding
of
Tribbles
family
pseudokinases
(TRIB1,
TRIB2
and
TRIB3)
reveal
these
proteins
as
potentially
valuable
biomarkers
disease
diagnosis,
prognosis,
prediction
clinical
strategy.
In
their
role
signalling
mediators
scaffolding
proteins,
TRIBs
lead
to
changes
protein
stability
activity,
which
impact
on
diverse
cellular
processes
such
proliferation,
differentiation,
cell
cycle
death.
We
review
TRIB
promising
therapeutic
targets,
with
an
emphasis
cancer,
biomarkers,
potential
application
across
pathological
processes.
Язык: Английский
Trib1 promotes acute myeloid leukemia progression by modulating the transcriptional programs of Hoxa9
Blood,
Год журнала:
2020,
Номер
137(1), С. 75 - 88
Опубликована: Июль 31, 2020
Язык: Английский