Abstract
Nrarp (Notch-regulated ankyrin repeat protein) is a small protein that has two ankyrin repeats1-5. Although Nrarp is known to be an inhibitory component of the Notch signalling pathway that operates in different developmental processes1,2,4,5, the in vivo roles of Nrarp have not been fully characterized. Here, we show that Nrarp is a positive regulator in the Wnt signalling pathway. In zebrafish, knockdown of Nrarp-a expression by an antisense morpholino oligonucleotide (MO) results in altered Wnt-signalling-dependent neural-crest-cell development. Nrarp stabilizes LEF1 protein, a pivotal transcription factor in the Wnt signalling cascade, by blocking LEF1 ubiquitination. In accordance with this, the knockdown phenotype of lef1 is similar to that of nrarp-a, at least in part, in its effect on the development of multiple tissues in zebrafish. Furthermore, activation of LEF1 does not affect Notch activity or vice versa. These findings reveal that Nrarp independently regulates canonical Wnt and Notch signalling by modulating LEF1 and Notch protein turnover, respectively.
| Original language | English |
|---|---|
| Pages (from-to) | 1106-1112 |
| Number of pages | 7 |
| Journal | Nature Cell Biology |
| Volume | 7 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2005 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability. / Ishitani, Tohru; Matsumoto, Kunihiro; Chitnis, Ajay B.; Itoh, Motoyuki.
In: Nature Cell Biology, Vol. 7, No. 11, 01.11.2005, p. 1106-1112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability
AU - Ishitani, Tohru
AU - Matsumoto, Kunihiro
AU - Chitnis, Ajay B.
AU - Itoh, Motoyuki
PY - 2005/11/1
Y1 - 2005/11/1
N2 - Nrarp (Notch-regulated ankyrin repeat protein) is a small protein that has two ankyrin repeats1-5. Although Nrarp is known to be an inhibitory component of the Notch signalling pathway that operates in different developmental processes1,2,4,5, the in vivo roles of Nrarp have not been fully characterized. Here, we show that Nrarp is a positive regulator in the Wnt signalling pathway. In zebrafish, knockdown of Nrarp-a expression by an antisense morpholino oligonucleotide (MO) results in altered Wnt-signalling-dependent neural-crest-cell development. Nrarp stabilizes LEF1 protein, a pivotal transcription factor in the Wnt signalling cascade, by blocking LEF1 ubiquitination. In accordance with this, the knockdown phenotype of lef1 is similar to that of nrarp-a, at least in part, in its effect on the development of multiple tissues in zebrafish. Furthermore, activation of LEF1 does not affect Notch activity or vice versa. These findings reveal that Nrarp independently regulates canonical Wnt and Notch signalling by modulating LEF1 and Notch protein turnover, respectively.
AB - Nrarp (Notch-regulated ankyrin repeat protein) is a small protein that has two ankyrin repeats1-5. Although Nrarp is known to be an inhibitory component of the Notch signalling pathway that operates in different developmental processes1,2,4,5, the in vivo roles of Nrarp have not been fully characterized. Here, we show that Nrarp is a positive regulator in the Wnt signalling pathway. In zebrafish, knockdown of Nrarp-a expression by an antisense morpholino oligonucleotide (MO) results in altered Wnt-signalling-dependent neural-crest-cell development. Nrarp stabilizes LEF1 protein, a pivotal transcription factor in the Wnt signalling cascade, by blocking LEF1 ubiquitination. In accordance with this, the knockdown phenotype of lef1 is similar to that of nrarp-a, at least in part, in its effect on the development of multiple tissues in zebrafish. Furthermore, activation of LEF1 does not affect Notch activity or vice versa. These findings reveal that Nrarp independently regulates canonical Wnt and Notch signalling by modulating LEF1 and Notch protein turnover, respectively.
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U2 - 10.1038/ncb1311
DO - 10.1038/ncb1311
M3 - Article
C2 - 16228014
AN - SCOPUS:33644828474
VL - 7
SP - 1106
EP - 1112
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 11
ER -