http:www'stanford'edurnussewntwindow'html

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Wnt Signaling
http//www.stanford.edu/rnusse/wntwindow.html Pan
dur, et al., 2003. Increasingly complex new
players enter the Wnt signaling
network.Bioessays. 2002 Oct24(10)881-4.
Review. Van Aken, et al., 2001. Defective
E-cadherin/catenin complexes in humna cancer.
Virchows Arch. 439725-751. Daniel, et al., 2001.
b-catenin molecular plasticity and drug design.
Trends Biochem. Sci. 26672-678. Malbon, et al.,
2001. Wnt signaling and heterotrimeric G
proteins. BBRC 287589-593. Jiang Mansel, 2000.
E-cadherin complex and its abnormalities in
breast cancer. Surgical Oncol. 9151-171. Peifer
Polakis Wnt signaling in oncogenesis and
embryogenesis--a look outside the nucleus.
Science. 2000 Mar 3287(5458)1606-9. Kikuchi A.
Regulation of beta-catenin signaling in the Wnt
pathway.Biochem Biophys Res Commun. 2000 Feb
16268(2)243-8 Seidensticker MJ, Behrens J.
Biochemical interactions in the wnt pathway.
Biochim Biophys Acta. 2000 Feb 21495(2)168-82.
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Cadherins maintain cell-cell adhesions
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Microfilament and Intermediate filament
associated cell-cell adhesions
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Fun Facts about b-Catenin
1. b-Catenin mediates interaction of cadherin
with actin at cell-cell adhesions. 2. b-Catenin
is Drosophila armadillo protein. Armadillo/
b-Catenin are downstream effectors of the
Wingless/Wnt signaling pathway. 3. Inhibition of
b-Catenin degradation during wnt signaling leads
to activation of Lef/Tcf transcription factors.
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Barish etal., 2000. Signaling networks and cell
cycle control, Ed. S. Gutkind, Humana Press, NJ
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Protein degradation by ubiquitination
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Activators of Wnt Signaling
Wnt/Wingless Ligand Frizzled Receptor ILK
Integrin Linked Kinase
Inhibitors of Wnt Signaling

• Secreted
• FRP/FRZB (Frizzled related protein)
• B. Control at the GSK3 (Glycogen Synthase kinase
  3) level
• APC, Adenomatous polyposis coli
• Dickopf
• Axin/Conductin
• Slimb/h-bTrCP

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APC in Wnt signaling
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Peifer Polakis, 2000. Science 2871606-1609.
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Wnt activates Frizzled
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Effectors of Wnt Signaling
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APC, Negative Regulator of Wnt Signaling
Seidensticker and Behrens, 2000. BBA 1495168-182
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Axin, Negative Regulator of Wnt Signaling
Seidensticker and Behrens, 2000. BBA 1495168-182
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Targeted degradation of b-catenin
Slimb
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Regulation of LEF-1/TCF transcription factors by
Wnt and other signals. Curr. Opin. Cell Biol.
11233-240.
b-catenin
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http//www.stanford.edu/rnusse/wntwindow.html
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Crosstalk
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The oncogenic activation of beta-catenin. Polakis,
1999. Curr. Op. Gen. Dev. 915-21
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Loss of E-cadherin expression is implicated in
tumor progression.
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