Uchida Daisuke, Omotehara Fumie, Nakashiro Koh-ichi, Tateishi Yoshihisa, Hino Satoshi, Begum Nasima-Mila, Fujimori Takahiro, Kawamata Hitoshi
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
Biochem Biophys Res Commun. 2003 Jun 13;305(4):846-54. doi: 10.1016/s0006-291x(03)00854-4.
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-beta 1. Moreover, the TSC-22 mRNA 3'-UTR destabilized the heterologous luciferase mRNA, but the destabilization was recovered with TGF-beta 1. These observations suggest that up-regulation of TSC-22 mRNA by TGF-beta 1 is achieved by mRNA stabilization, but not by transcriptional activation.
TSC - 22基因由三个外显子组成，其长度约为5.5 kb，包括2.9 kb的启动子区域。转录起始位点位于TATA框下游7和29 bp处。启动子分析表明，TSC - 22启动子的2146 bp被几种分化诱导药物激活。虽然TSC - 22最初是作为一种TGF - β诱导基因分离出来的，但TSC - 22启动子并未被增强的TGF - β信号激活。我们在人TSC - 22 mRNA 3'-UTR中发现了3个Shaw - Kamens序列(AUUUA)，并鉴定出三种与之结合的蛋白质(40、20和15 kDa)。仅用TGF - β 1处理可使40 kDa蛋白质 - RNA复合物减少。此外，TSC - 22 mRNA 3'-UTR使异源荧光素酶mRNA不稳定，但用TGF - β 1可恢复这种不稳定状态。这些观察结果表明，TGF - β 1对TSC - 22 mRNA的上调是通过mRNA稳定实现的，而不是通过转录激活。
