Clusterin, a novel modulator of TGF-beta signaling, is involved in Smad2/3 stability.

Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. It is known that CLU interacts with TGF-beta type ll receptor (TbetaRll). However, the relationship of CLU and TGF-beta signaling is unclear. Here we present that CLU is a novel modulator of TGF-beta signaling by regulating Smad2/3 proteins. Overexpression of CLU enhanced TGF-beta-induced transcriptional activity and increased the amount of Smad2/3 proteins, while CLU siRNA repressed TGF-beta-induced transcriptional activity and decreased the amount of Smad2/3 proteins in Hep3B cells. We also found that CLU was involved in Smad2/3 stability at the protein level. These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins.