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0:00
My name is David Virshup.
I'm a professor
in the Program in
Cancer and Stem Cell Biology at
the Duke-NUS Medical
School in Singapore.
Today, I'm going
to tell you about
the Wnt signaling pathway.
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So, one important thing
in any scientific lecture
is this saying that I
learned when I was back
in medical school.
"Half of what I'm going to
tell you today is wrong,
half of it is right. I don't
know which half is which."
As in anything in the scientific
process, it's a process.
We get it right most of the
time and then we go back
and correct things later
when we figure out
what was wrong.
So, take everything
with a grain of salt,
but I will tell you
today the way we
think the Wnt signaling
pathway happens.
0:45
So, in the Wnt signaling pathway
in its core incarnation,
Wnts are made in a cell that
sends Wnts to another cell.
I have a Wnt sending cell
as you see on the left,
and that cell produces Wnts,
which is shown there in yellow.
Those Wnts are
post-translationally
modified by an enzyme
called porcupine (PORCN),
we'll talk more about later
that allows the Wnts to bind to
a transporter protein
called Wntless,
which just appeared,
and then the Wnts
are carried off and transported
somehow to the Wnt 'receiving'
cell where they bind
to a pair of receptor and
coreceptor on the
plasma membrane.
That sets up the
signaling pathway
that stabilizes a protein
called β-catenin,
which is part of the β-catenin
destruction complex,
and then β-catenin
because it's accumulating
can move to the
nucleus of the cell
bind to a transcriptional
repressor called TCF or Lef,
derepress it and turn on a
variety of target genes,
some of which are
well-understood
and others which are
very tissue-specific.
