FOXKs Promote Wnt/β-catenin Signaling by Translocating DVL into the Nucleus

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2015 Mar 26

PMID 25805136

Citations 76

Authors

Wenqi Wang

Xu Li

Moonsup Lee

Sohee Jun

Kathryn E Aziz

Lin Feng

My Kim Tran

Nan Li

Pierre D McCrea

Jae-Il Park

Junjie Chen

Affiliations

Soon will be listed here.

Abstract

Dishevelled (DVL) proteins serve as crucial regulators that transduce canonical Wnt signals to the GSK3β-destruction complex, resulting in the stabilization of β-catenin. Emerging evidence underscores the nuclear functions of DVLs, which are critical for Wnt/β-catenin signaling. However, the mechanism underlying DVL nuclear localization remains poorly understood. Here we discovered two Forkhead box (FOX) transcription factors, FOXK1 and FOXK2, as bona fide DVL-interacting proteins. FOXK1 and FOXK2 positively regulate Wnt/β-catenin signaling by translocating DVL into the nucleus. Moreover, FOXK1 and FOXK2 protein levels are elevated in human colorectal cancers and correlate with DVL nuclear localization. Conditional expression of Foxk2 in mice induced intestinal hyper-proliferation that featured enhanced DVL nuclear localization and upregulated Wnt/β-catenin signaling. Together, our results not only reveal a mechanism by which DVL is translocated into the nucleus but also suggest unexpected roles of FOXK1 and FOXK2 in regulating Wnt/β-catenin signaling.

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