PMC:3586680 / 7511-9219 JSONTXT

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WWOX also binds PPxY motif-containing transcription factors, such as RUNX2, c-Jun, and ERBB4, via its first WW domain, and the binding blocks the activity of these proteins by retaining them in the cytoplasm. WWOX binds Tau via its SDR domain. WWOX participates in the Wnt/β-catenin signal pathway by binding Dvl and inhibiting its nuclear import. Phorbol ester stimulates the dissociation of MEK/WWOX complex in Jurkat T cell, and the released WWOX translocates to the mitochondria for causing cell death. WWOX is recruited to the membrane area by association with Hyal-2 and phospho-Ezrin. Hyal-2 is an alternative receptor for TGF-β1. In response to TGF-β1, WWOX binds Hyal-2 and forms a complex, followed by relocating to the nucleus and enhancing the SMAD-driven promoter activity. 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