O-GlcNAcylation of FBP1 promotes pancreatic cancer progression by facilitating its Lys48-linked polyubiquitination in hypoxic environments
Abstract
Fructose-1,6-bisphosphatase
1
(FBP1),
a
rate-limiting
enzyme
in
gluconeogenesis,
is
important
for
cancer
progression.
The
post-translational
regulation
of
FBP1
hypoxic
environments
still
unclear.
Here,
we
report
that
down-regulated
and
low
expression
level
predicts
poor
prognosis
pancreatic
cancer.
Hypoxic
environment
makes
more
prone
to
degradation
this
effect
can
be
reversed
by
inhibiting
global
O-GlcNAcylation
signalling.
O-linked
N-acetylglucosamine
transferase
(OGT)
interact
with
induce
its
at
serine
47
residue
(FBP1-S47)
modulate
protein
function
cell.
FBP1-S47
promote
also
influence
the
canonical
HIF-1α
target
genes
involved
glucose
metabolism,
resulting
an
increase
uptake
lactate
secretion
cells.
In
addition,
facilitates
K48-linked
polyubiquitination
lysine
51
(FBP1-K51),
which
GlcNAc
moiety
serve
as
prerequisite
ubiquitin
ligase.
(K51)
mediated
progression
similarly
FBP1-S47.
Our
data
uncover
mechanism
whereby
regulated
O-GlcNAcylation-polyubiquitination
axis,
paving
way
cell
metabolic
reprogram.
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 11, 2024
Язык: Английский