Scribble Regulates the Nucleus Entry of β-catenin

Abstract: Scribble (Scrib) is a member of the leucinerich repeat and PDZ containing protein ( LAP ) family， connected to the membrane. Scrib plays a variety of roles by combinating with many protein molecules and integrating multiple signaling pathways in scaffolding protein ways. β-catenin a multifunctional protein， plays central roles in mediating cell adhesion and signal transduction. To study what relationship and regulative mechanism between Scrib and β-catenin， we have done a series of experiments. We found that after Scrib was overexpressed in HEK293/ HEK293T， the transcriptional activity of β-catenin， the LEF-1-luciferase activity of the reporter gene was significantly reduced; while after Scrib was stably reduced in the HEK293/HEK293T， the LEF-1-luciferase activity of the reporter gene was significantly increased. So we can conclude that Scrib can inhibit the transcriptional activity of β- catenin. We also found that Scrib could specially interact with β-catenin by endogenous Co-IP. Furthermore， in cellular separation experiments of HEK293/293T， we found after Scrib was stably reduced， total cellular β-catenin wasn’t affected， while the cytoplasmic and nucleus β-catenin was increased. We showed Scrib could inhibit the nucleus entry of β-catenin. We herein demonstrate that the molecular mechanism between hScrib and β-catenin: Scrib could interact with β-catenin and inhibit the nucleus entry of β-catenin， thus inhibiting the downstream gene regulation of β-catenin.

CSTR: 32200.14.cjcb.2010.03.0017