Jerky/Earthbound facilitates cell-specific Wnt/Wingless signalling by modulating β-catenin-TCF activity

• Published in: The EMBO journal Vol. 30; no. 8; pp. 1444 - 1458
• Main Authors: Benchabane, Hassina, Xin, Nan, Tian, Ai, Hafler, Brian P, Nguyen, Kerrie, Ahmed, Ayah, Ahmed, Yashi
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 20-04-2011; Nature Publishing Group UK; Nature Publishing Group
• Subjects: Animals; Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; beta Catenin - genetics; beta Catenin - metabolism; Blotting, Western; cell context; Cells, Cultured; Centromere Protein B - genetics; Centromere Protein B - metabolism; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Drosophila - genetics; Drosophila - growth & development; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; EMBO11; EMBO37; Humans; Immunoenzyme Techniques; Immunoprecipitation; Kidney - cytology; Kidney - metabolism; Luciferases - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction; TCF; TCF Transcription Factors - genetics; TCF Transcription Factors - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Wnt; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt1 Protein - genetics; Wnt1 Protein - metabolism; β-catenin; β‐catenin; Wnt; cell context; signal transduction; TCF
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2011.67

Wnt/Wingless signal transduction directs fundamental developmental processes, and upon hyperactivation triggers colorectal adenoma/carcinoma formation. Responses to Wnt stimulation are cell specific and diverse; yet, how cell context modulates Wnt signalling outcome remains obscure. In a Drosophila genetic screen for components that promote Wingless signalling, we identified Earthbound 1 (Ebd1), a novel member in a protein family containing Centromere Binding Protein B (CENPB)‐type DNA binding domains. Ebd1 is expressed in only a subset of Wingless responsive cell types, and is required for only a limited number of Wingless‐dependent processes. In addition, Ebd1 shares sequence similarity and can be functionally replaced with the human CENPB domain protein Jerky, previously implicated in juvenile myoclonic epilepsy development. Both Jerky and Ebd1 interact directly with the Wnt/Wingless pathway transcriptional co‐activators β‐catenin/Armadillo and T‐cell factor (TCF). In colon carcinoma cells, Jerky facilitates Wnt signalling by promoting association of β‐catenin with TCF and recruitment of β‐catenin to chromatin. These findings indicate that tissue‐restricted transcriptional co‐activators facilitate cell‐specific Wnt/Wingless signalling responses by modulating β‐catenin–TCF activity.
Cell type‐specific interpretation of Wnt/β‐catenin signals is a major unanswered question in developmental biology. This paper characterizes Ebd/Jerky, a member of the family of DNA‐binding CENPB domain proteins as new tissue‐specific and positive regulator of this developmental and tumour‐relevant pathway.