The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway."

SCRIB is a scaffold protein containing leucine-rich repeats (LRR) and PSD-95/Dlg-A/ZO-1 domains (PDZ) which localizes at the basolateral membranes of polarized epithelial cells. Deregulation of its expression or localization leads to epithelial defects and tumorigenesis in part as a consequence of its repressive role on several signaling pathways including AKT, ERK and HIPPO. In the present work, we used a proteomic approach to characterize the protein complexes associated to SCRIB and its paralogue LANO. We identified common and specific sets of proteins associated to SCRIB and LANO by mass spectrometry and provide an extensive landscape of their associated networks, and the first comparative analysis of their respective interactomes. Under proteasome inhibition, we further found that SCRIB was associated to the β-catenin destruction complex which is central in Wnt/β-catenin signaling, a conserved pathway regulating embryonic development and cancer progression. We show that the SCRIB/β-catenin interaction is potentiated upon Wnt3a stimulation and that SCRIB plays a repressing role on Wnt signaling. Our data thus provide evidence for the importance of SCRIB in the regulation of the Wnt/β-catenin pathway. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: Proteomics
ISSN: 1615-9861
Pages: e1800487


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A catenin that binds F-ACTIN and links the CYTOSKELETON with BETA CATENIN and GAMMA CATENIN.

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