title: Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ser Sur
authors.initials: SS
authors.lastname: Ng
authors.forename: Fangli
authors.initials: F
authors.lastname: Ren
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Duan
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Yonggong
authors.initials: Y
authors.lastname: Zhai
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: 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*
chemical_list: 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