TIF1β在α1-酸性醣蛋白基因調控之研究

Abstract

核受體屬於配基-誘發性的轉錄因數，其在與認知的反應區結合後可調節標的基因的表現；核受體的配基-依賴性活化功能，AF-2 ，推測可經由轉錄介子/中間因數作用在基本的轉錄機構上。雖然中間因數(介子)顯現居間傳導核受體的活化功能，但是對於這個由核受體引發的轉錄性活化的分子機轉仍不瞭解。筆者由小鼠基因庫中篩選到 TIF1β這個核蛋白，並證實它在試管中可與醣皮激素受體交互作用。在哺乳動物細胞，予以配基刺激，可促進小鼠乳腺腫瘤病毒-和α1-酸性醣蛋白-氯黴素乙醯基轉移?基因的表現。因此TIF1β很可能是一個有關媒介醣皮質激素受體荷爾蒙結合區活化功能的共活子。

Nuclear receptors (NRs) act as ligand-inducible transcription factors which regulate the expression of target genes upon binding to their cognate response elements. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through transcriptional mediators/intermediary factors (TIFs). But the molecular mechanisms underlying transcriptional activation by NRs are still poorly understood, although intermediary factors (mediators) appear to be involved in mediating the transactivation functions of NRs. We have isolated the cDNA encoding mouse nuclear proteins, TIF1β, that can interact with the glucocorticoid receptor (GR) in vitro. Overexpression of the TIF1β gene in mammalian cells enhances the hormone-regulated expression of mouse mammary tumor virus- and α1-acid glycoprotein- chloramphenical acetyltransferase gene. Thus TIF1β can probably serve as a coactivator, potentiating the transactivation functions in glucocorticoid receptor hormone binding domain (HBD).