Wang Z, Melmed S
Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA.
J Biol Chem. 2000 Mar 17;275(11):7459-61. doi: 10.1074/jbc.275.11.7459.
Pituitary tumor transforming gene (PTTG) is a newly identified transforming gene, the functional mechanism of which is little understood. Computational analysis reveals a C terminus rich in Glu and Pro, a known characteristic of transcriptional activation domains. We report here that murine PTTG indeed possesses transactivation ability, which correlates highly with its transforming properties. Pro(139), Ser(159), Pro(157)-Pro(158)-Ser(159)-Pro(160) (PPXP motif), and Leu(120)-Asp(121)-Phe(122)-Asp(123)-Leu(124) were found to be important for transactivation. Mutation to Ala at a key Pro(139) residue not only disrupted the transactivation function but also resulted in the loss of transforming ability in NIH3T3 cells. A murine PTTG cDNA that encodes a variant C-terminal tail (Gly-Lys-Gly-Val-Arg-Ser-Asn-Gly-Cys-Lys-Asp-Leu-Val-Thr) was cloned. This novel PTTG is devoid of transactivation and transforming ability; deletion of its variant C-terminal tail restores both transactivation and transforming ability. These results show a high correlation between the transforming and transactivation functions of PTTG and also indicate that the novel PTTG variant may function as an endogenous competitor to wild-type PTTG.
垂体肿瘤转化基因（PTTG）是一种新发现的转化基因，其功能机制尚不清楚。计算分析显示其C末端富含谷氨酸和脯氨酸，这是转录激活域的一个已知特征。我们在此报告，小鼠PTTG确实具有反式激活能力，这与其转化特性高度相关。发现Pro（139）、Ser（159）、Pro（157）-Pro（158）-Ser（159）-Pro（160）（PPXP基序）和Leu（120）-Asp（121）-Phe（122）-Asp（123）-Leu（124）对反式激活很重要。关键的Pro（139）残基突变为丙氨酸不仅破坏了反式激活功能，还导致NIH3T3细胞转化能力丧失。克隆了一个编码可变C末端尾巴（Gly-Lys-Gly-Val-Arg-Ser-Asn-Gly-Cys-Lys-Asp-Leu-Val-Thr）的小鼠PTTG cDNA。这种新型PTTG缺乏反式激活和转化能力；缺失其可变C末端尾巴可恢复反式激活和转化能力。这些结果表明PTTG的转化和反式激活功能之间高度相关，也表明新型PTTG变体可能作为野生型PTTG的内源性竞争者发挥作用。
