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.
Lee
Kwan-Bok
KB
School of Bioscience and Biotechnology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Jeon
Jun-Ho
JH
Choi
Inpyo
I
Kwon
O-Yu
OY
Yu
Kweon
K
You
Kwan-Hee
KH
D045744:Cell Line, Tumor; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C495242:CLU protein, human; D051152:Clusterin; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta