Pituitary tumor transforming gene (PTTG) transforming and transactivation activity

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.