Smad4 cooperates with lymphoid enhancer-binding factor 1/T cell-specific factor to increase c-myc expression in the absence of TGF-beta signaling.

ABSTRACT: The c-myc protooncogene is a key regulator of cell proliferation whose expression is reduced in normal epithelial cells in response to the growth inhibitory cytokine TGF-beta. Smad4 mediates this inhibitory effect of TGF-beta by forming a complex with Smad3, E2F4/5, and p107 at the TGF-beta inhibitory element (TIE) element on the c-myc promoter. In contrast, cell proliferation and c-myc expression are increased in response to Wnt ligands; this effect is mediated through the lymphoid enhancer-binding factor 1/T cell-specific factor (LEF/TCF) family of transcription factors on the c-myc promoter LEF/TCF-binding elements (TBE1 and TBE2). We report that a peptide aptamer designed to inhibit the binding between Smad4 and LEF/TCF reduced c-myc expression and the growth rate of HepG2 cells. Furth

SUBMITTER: Lim SK 

PROVIDER: S-EPMC1693705 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature