Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation.
Tsc-22 was isolated as a TGF-beta-inducible gene by differential screening of the mouse osteoblastic cell cDNA library [J Biol Chem 267 (1992) 10219]. tsc-22 mRNA is expressed in almost all organs of mice and humans and its expression is induced in a variety of cell lines by many different factors including TGF-beta, phorbol ester, serum, and progestin. tsc-22 encodes a 18-kd protein that contains a leucine zipper motif and a Tsc-box. The leucine zipper motif of the Tsc-22 protein does not have a basic DNA binding motif and when the protein was fused to a heterologous DNA binding domain, it showed various transcription-modulating activities ranging from activation to repression [J Biol Chem 274 (1999) 27439, Biochem Biophys Res Commun 278 (2000) 659]. Although these results suggest that the Tsc-22 protein functions as a transcriptional regulator recruiting various coactivators or repressors, its mechanism is not known. In this study, we examined whether Tsc-22 modulates the TGF-beta-dependant signaling pathway and found that Tsc-22 binds to and modulate the transcriptional activity of Smad3 and Smad4. Its effect on cellular differentiation was also examined.
Choi
So-Jung
SJ
Department of Molecular Cell Biology and Center for Molecular Medicine, SBRI, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Moon
Jae-Hoon
JH
Ahn
Young-Wook
YW
Ahn
Jin-Hyun
JH
Kim
Dong-Uk
DU
Han
Tae-Hee
TH
D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D009154:Mutation; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; C099726:TSC22D1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta