SIGNALING FROM POLYOMAVIRUS MIDDLE-T AND SMALL-T DEFINES DIFFERENT ROLES FOR PROTEIN PHOSPHATASE 2A

Polyomavirus causes a broad spectrum of tumors as the result of the ac tion of its early proteins. This work compares signaling from middle T antigen (MT), the major transforming protein, to that from small T an tigen (ST). The abilities of MT mutants to promote cell cycle progress ion in serum-starved NIH 3T3 cells were compared. Transformation-defec tive mutants lacking association with SMC or with phosphatidylinositol 3-kinase (PI3-K) retained the ability to induce DNA synthesis as meas ured by bromodeoxyuridine incorporation, Only when both interactions w ere lost in the Y250F/Y315F double mutant was MT inactive, ST promoted cell cycle progression in a manner dependent on its binding of protei n phosphatase 2A (PP2A). Since the Y250F/Y315F MT mutant was wild type for PP2A binding yet unable to promote cell cycle progression, while ST was capable of promoting cell cycle progression, these experiments revealed a functional difference in MT and ST signaling via PP2A. Assa ys testing the abilities of MT and ST to induce the c-fos promoter and to activate c-jun kinase led to the same conclusion. ST, but not Y250 /Y315F MT, was able to activate the c-fos promoter through its interac tion with PPM. In contrast, MT, but not ST,,vas able to activate c-jun kinase by virtue of its interaction with PPM.