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FMRP recruitment of β‐catenin to the translation pre‐initiation complex represses translation
Author(s) -
Ehyai Saviz,
Miyake Tetsuaki,
Williams Declan,
Vinayak Jyotsna,
Bayfield Mark A,
McDermott John C
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745536
Subject(s) - translation (biology) , biology , microbiology and biotechnology , catenin , genetics , eukaryotic translation , computational biology , signal transduction , messenger rna , gene , wnt signaling pathway
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 ( VSMC s), 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.