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Fig. 4. Notch modulates Wnt pathway transcriptional activity in both
Drosophila and vertebrate cells. (A) Diagram of the Notch molecules
used. (B) Ectopic activation of the Wnt signalling pathway was observed in
Drosophila clone8 (cl8) cells in the presence of Notch dsRNA
(104-fold activation compared to no dsRNA), but not GFP dsRNA (1.1-fold
activation). (C,D) In Drosophila SL2 (C), or S2R+ cells
(D) Wnt signalling was induced with an oncogenic form of ß-catenin, S37A
ß-catenin (Schweizer and Varmus,
2003), the presence of a membrane tethered form of Notch (TNotch)
significantly reduced the level of ectopic Wnt signalling (C,D). (E-H)
N-N1 (delN-N1) cleaves spontaneously to release the NICD domain of
Notch1 as shown by the strong activation of the CBF1 reporter (H), whereas
LNR-N1 rarely cleaves as shown by the weak activation of the CBF1 reporter (H)
(Mumm et al., 2000). A further
inhibitor of Wnt signalling ExFz8 acts by titrating Wnt
(Brennan et al., 2004). Ectopic
Wnt signalling was induced with Wnt1, delN-LRP6, Dishevelled, activated
ß-catenin or LEF1-VP16 in HEK-293T cells. Both forms of Notch are capable
of significantly repressing ectopic Wnt signalling induced by Wnt1, Dsh, and
activated ß-catenin (E,F), LNR-N1 effects extended to ectopic Wnt
signalling induced by delN-LRP6 and LEF1-VP16. Whereas, ExFz8 repressed
ectopic Wnt signalling induced by Wnt1, some small effects on the
intracellular mediators of Wnt signalling were observed, such effects have
previously been reported (Suzuki et al.,
2004) (G).
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