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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.

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This article was published in the following journal.

Name: Proteomics
ISSN: 1615-9861
Pages: e1800487

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Medical and Biotech [MESH] Definitions

A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, which when mutated results in the wingless phenotype, and the vertebrate INT gene, which is located near integration sites of MOUSE MAMMARY TUMOR VIRUS. The signaling pathway is initiated by the binding of WNT PROTEINS to cells surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.

A specific complex of WNT SIGNALING PATHWAY proteins that mediates the phosphorylation-dependent destruction of cytosolic BETA-CATENIN. The complex is disrupted by cell surface binding of WNT PROTEINS, which allows beta-catenin levels to rise to the point where they migrate to the CELL NUCLEUS and activate transcription.

A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS1 functions as a negative regulator of CYTOKINES that signal through the JANUS KINASES-STAT 3 TRANSCRIPTION FACTOR (JAK/STAT3) pathway by inhibiting the activity of JANUS KINASES.

A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.

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

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