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Proteasomal activity modulates TGF-ss signaling in a gene-specific manner
Fan Zhang1, Mia Mönkkönen, Stina Roth
1Haartman Institute, Department of Virology and Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, P.O. Box 63, FIN-00014, Helsinki, Finland.
Abstract:
Transforming growth factor-beta (TGF-beta) signaling relies on Smad-signaling pathway controlled in part by the proteasome. Here we demonstrate that inhibition of the proteasome function in mink epithelial cells accumulates both positive and negative modulators of TGF-beta signaling, phospho-Smad2 and SnoN. Inhibition of the proteasome led to abrogation of TGF-beta target gene regulation in a gene-specific manner. While regulation of p15Ink4b and myc by TGF-beta are lost, PAI-1 induction, previously shown to occur in a Smad3-dependent manner, was not affected by treatment of the cells with the proteasomal inhibitor MG132. The results suggest that proteasomal activity is required for TGF-beta signaling in a gene-specific manner.