Logo image
Back
Centrosomes are required for proper β-catenin processing and Wnt response
Journal article   Open access   Peer reviewed

Centrosomes are required for proper β-catenin processing and Wnt response

Setu M Vora, Jan S Fassler and Bryan T Phillips
Molecular biology of the cell, Vol.31(17), pp.1951-1961
08/01/2020
DOI: 10.1091/mbc.E20-02-0139
PMCID: PMC7525817
PMID: 32583737
url
https://doi.org/10.1091/mbc.E20-02-0139View
Published (Version of record) Open Access

Abstract

The Wnt/β-catenin signaling pathway is central to metazoan development and routinely dysregulated in cancer. Wnt/β-catenin signaling initiates transcriptional reprogramming upon stabilization of the transcription factor β-catenin, which is otherwise posttranslationally processed by a destruction complex and degraded by the proteasome. Since various Wnt signaling components are enriched at centrosomes, we examined the functional contribution of centrosomes to Wnt signaling, β-catenin regulation, and posttranslational modifications. In HEK293 cells depleted of centrosomes we find that β-catenin synthesis and degradation rates are unaffected but that the normal accumulation of β-catenin in response to Wnt signaling is attenuated. This is due to accumulation of a novel high-molecular-weight form of phosphorylated β-catenin that is constitutively degraded in the absence of Wnt. Wnt signaling operates by inhibiting the destruction complex and thereby reducing destruction complex–phosphorylated β-catenin, but high-molecular-weight β-catenin is unexpectedly increased by Wnt signaling. Therefore these studies have identified a pool of β-catenin effectively shielded from regulation by Wnt. We present a model whereby centrosomes prevent inappropriate β-catenin modifications that antagonize normal stabilization by Wnt signals.

Details

Metrics

13 Record Views
8 Times Cited - Web of Science
Logo image