title: Myc-interacting zinc-finger protein 1 positively regulates Wnt signalling by protecting Dishevelled from Dapper1-mediated degradation.
abstract: Wnt signalling regulates embryonic development and tissue homoeostasis by modulating cell proliferation, differentiation and migration. Dapper1 (Dpr1) has been shown to be an important key negative regulator of Wnt signalling by promoting Dishevelled (Dvl) degradation. In the present study, we found that Myc-interacting zinc-finger protein 1 (MIZ1) interacts with Dpr1 and this interaction attenuates the ability of Dpr1 to induce Dvl2 degradation, thus enhancing Wnt signalling. Mechanistically, MIZ1 is translocated from the nucleus to the cytoplasm upon Wnt3a stimulation or overexpression of Dpr1 and Dvl2, disrupting the interaction between Dpr1 and Dvl2. Furthermore, MIZ1 can promote the proliferation of breast cancer MDA-MB-231 and BT-549 cells through Wnt signalling and reverse the anti-proliferative effect of Dpr1 on colorectal cancer Caco-2. Together, our findings establish a novel layer of Wnt signalling regulation via the MIZ1-Dpr1-Dvl axis.
authors.affiliation: *The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: *The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: *The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: *The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: *The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D000072261:Dishevelled Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491683:DACT1 protein, human; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; C107961:ZBTB17 protein, human