Abstract
Canonical Wnt/β‐catenin signaling is an essential regulator of various cellular functions throughout development and adulthood. Aberrant Wnt/β‐catenin signaling also contributes to various pathologies including cancer, necessitating an understanding of cell context‐dependent mechanisms regulating this pathway. Since protein–protein interactions underpin β‐catenin function and localization, we sought to identify novel β‐catenin interacting partners by affinity purification coupled with tandem mass spectrometry in vascular smooth muscle cells (VSMCs), where β‐catenin is involved in both physiological and pathological control of cell proliferation. Here, we report novel components of the VSMC β‐catenin interactome. Bioinformatic analysis of the protein networks implies potentially novel functions for β‐catenin, particularly in mRNA translation, and we confirm a direct interaction between β‐catenin and the fragile X mental retardation protein (FMRP). Biochemical studies reveal a basal recruitment of β‐catenin to the messenger ribonucleoprotein and translational pre‐initiation complex, fulfilling a translational repressor function. Wnt stimulation antagonizes this function, in part, by sequestering β‐catenin away from the pre‐initiation complex. In conclusion, we present evidence that β‐catenin fulfills a previously unrecognized function in translational repression.
Synopsis

This study reports novel components of the β‐catenin interactome and identifies an β‐catenin/FMRP (fragile X mental retardation protein) complex with translational repressor function.
Biochemical studies reveal recruitment of β‐catenin/FMRP to the translational pre‐initiation complex, fulfilling a translational repressor function.
Wnt‐3a stimulation promotes β‐catenin re‐localization to the nucleus and concomitant de‐repression of translation.
EMBO Reports (2018) e45536
- Received November 23, 2017.
- Revision received September 12, 2018.
- Accepted September 19, 2018.
- © 2018 The Authors
Subscribers, please sign in with your username and password.
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
EMBO Members please login here to access the journals
Subscribe to the Journal
Recommend to your Librarian