TSC-22 gene was composed of three exons and its length was approximately 5.5 kb including 2.9 kb promoter region. The transcription starting site was located at 7 and 29 bp downstream from TATA box. Promoter analysis revealed that 2146 bp of TSC-22 promoter was activated by several differentiation inducing drugs. Although originally TSC-22 was isolated as a TGF-beta-inducible gene, TSC-22 promoter was not activated by the enhanced TGF-beta signaling. We found 3 copies of the Shaw-Kamens sequence (AUUUA) in the human TSC-22 mRNA 3'-UTR and identified three proteins (40, 20, and 15 kDa) which bound to this. Only the 40 kDa protein-RNA complex was decreased by treatment with TGF-beta1. Moreover, the TSC-22 mRNA 3'-UTR destabilized the heterologous luciferase mRNA, but the destabilization was recovered with TGF-beta1. These observations suggest that up-regulation of TSC-22 mRNA by TGF-beta1 is achieved by mRNA stabilization, but not by transcriptional activation. (C) 2003 Elsevier Science (USA). All rights reserved.