Identification and characterization of a novel Dvl-binding protein that suppresses Wnt signalling pathway.
BACKGROUND
Dvl is a cytoplasmic protein to regulate the stability of beta-catenin in the Wnt signalling pathway. However, the molecular mechanism by which Dvl regulates the Wnt signalling pathway is not fully understood.


RESULTS
We identified a novel protein that binds to Dvl and named it Daple. Daple consisted of 2009 amino acids with a high frequency of leucine residues and formed a homo-oligomer. The C-terminal three amino acids of Daple were necessary for binding to the region containing the PDZ domain of Dvl. Expression of Daple in mouse fibroblast L cells inhibited Wnt-3a-induced accumulation of beta-catenin. Furthermore, Daple inhibited Wnt-3a-dependent activation of T-cell factor (Tcf) transcriptional activity. Expression of Daple in the dorsal region of Xenopus embryos inhibited axis formation, which is known to be regulated by the Wnt signalling pathway. Daple also inhibited Dvl-induced secondary axis formation in Xenopus embryos.


CONCLUSIONS
Daple binds to Dvl and functions as a negative regulator of the Wnt signalling pathway.
Oshita
Akihiko
A
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
Kishida
Shosei
S
Kobayashi
Hiroki
H
Michiue
Tatsuo
T
Asahara
Toshimasa
T
Asashima
Makoto
M
Kikuchi
Akira
A
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; C490440:Daple protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C555506:WNT3A protein, Xenopus; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D029867:Xenopus Proteins; D051176:beta Catenin