Reactome: A Curated Pathway Database

Beta-catenin binds SOX proteins

Stable Identifier
R-HSA-5626938
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

SOX protein family members are the transcription factors that regulate many different development processes and also control homeostasis in adult tissues. SOX proteins can be either transcriptional activators or repressors depending on the cellular context and their associated interacting proteins (Kormish et al. 2010). There are over twenty SOX proteins encoded in mammalian genome of which many of these can physically interact with beta-catenin and TCF (T-cell factor) transcription factors and modulate the Wnt signaling. Evidences suggest that SOX proteins have widespread role in modulating Wnt signaling in development and disease. In most cases SOX proteins repress WNT transcriptional responses, however some SOX proteins appear to enhance WNT-regulated gene expression. The precise mechanism by which SOX proteins regulate beta-catenin/TCF activity are still unclear. Differential recruitment of transcriptional co-activators or co-repressors is one mechanism by which SOX factors can either enhance or repress Wnt-target gene transcription. Another mechanism by which some SOX proteins repress Wnt signaling is by promoting proteosome-mediated beta-catenin degradation (Kormish et al. 2010).
Human SRY binds beta-catenin through a N-terminal domain (Bernard et al. 2008), SOX6 interacts via a centrally located leucine zipper (LZ/Q) element (Iguchi et al. 2007), and mammalian SOX7, SOX9 and SOX17 all bind beta-catenin via their C-terminal regions (Zorn et al., 1999; Takash et al., 2001; Akiyama et al., 2004; Sinner et al., 2007, Kormish et al. 2010). SRY and SOX9 function in part by suppressing canonical Wnt signaling by promoting beta-catenin phosphorylation in the nucleus (Topol et al. 2009). SOX9 and SRY are involved in the regulation of mammalian sex determination and mutation in human SRY and SOX9 results in sex reversal, with female development in XY individuals (Bernard et al. 2008). SOX2 binds beta-catenin and promotes cell proliferation by transcriptionally activating the Wnt target Cyclin D1 gene in breast cancer cells (Chen et al., 2008), whereas SOX6 represses Cyclin D1 transcription in pancreatic cells (Iguchi et al., 2007). SOX7 and SOX17 reduce cyclin-D1 expression and repress proliferation by stimulating beta-catenin degradation (Sinner et al. 2007, Zhang et al. 2008, 2009).

Literature References
PubMed ID Title Journal Year
17698607 Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium J. Cell Biol. 2007
18456656 The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer J. Biol. Chem. 2008
17875931 Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells Mol. Cell. Biol. 2007
17412698 SOX6 suppresses cyclin D1 promoter activity by interacting with beta-catenin and histone deacetylase 1, and its down-regulation induces pancreatic beta-cell proliferation J. Biol. Chem. 2007
11691915 SOX7 transcription factor: sequence, chromosomal localisation, expression, transactivation and interference with Wnt signalling Nucleic Acids Res. 2001
19047045 Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus J. Biol. Chem. 2009
18819930 Sox7 Is an independent checkpoint for beta-catenin function in prostate and colon epithelial cells Mol. Cancer Res. 2008
10549281 Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin Mol. Cell 1999
18598779 Human SRY inhibits beta-catenin-mediated transcription Int. J. Biochem. Cell Biol. 2008
15132997 Interactions between Sox9 and beta-catenin control chondrocyte differentiation Genes Dev. 2004
17218525 Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13 Science 2007
24291232 ?-Catenin, a Sox2 binding partner, regulates the DNA binding and transcriptional activity of Sox2 in breast cancer cells Cell. Signal. 2014
Participants
Participant Of
Orthologous Events