Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex.
The TCF4/beta-catenin complex, the executor of canonical Wnt/beta-catenin signaling, is regulated by a variety of factors. Among these, Dishevelled (Dvl) is a critical regulator that releases beta-catenin from degradation and stabilizes TCF4/beta-catenin complex. Here, we report that DDIP (Dishevelled-DEP domain Interacting Protein, also named as Spats1, spermatogenesis associated, serine-rich 1), a novel protein that interacts with Dvl, regulates Wnt signaling. We provide evidence that DDIP suppresses Lef-1 luciferase reporter activity stimulated by Wnt1, Dvl2 or beta-catenin, interacts with the TCF4/beta-catenin complex, and disrupts the interaction of TCF4 and beta-catenin by promoting TCF4 degradation through the proteasome pathway. Our results indicate that DDIP is a negative regulator of the canonical Wnt signaling.
Zhang
Haiwei
H
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
Zhang
Hui
H
Zhang
Yanquan
Y
Ng
Ser Sur
SS
Ren
Fangli
F
Wang
Yingying
Y
Duan
Yaqi
Y
Chen
Lin
L
Zhai
Yonggong
Y
Guo
Qinglong
Q
Chang
Zhijie
Z
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D000072261:Dishevelled Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D051155:Wnt1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C554273:SPATS1 protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin