Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation

The high risk human papillomavirus (HPV) type 16 E7 protein affects cell gr owth control and promotes transformation by interfering with functions of c ellular proteins. A keg target of E7 is the tumor suppressor protein p105RB . Although this interaction is required for E7-dependent transformation, ot her cellular molecules must also be involved, because some E7 mutants that have reduced transforming abilities still bind to p10RB. In order to identi fy additional proteins that interact with E7 and that may be responsible to mediate its transforming function, we have used the C-terminal half of E7 in a yeast two-hybrid screen. We identified the fork head domain transcript ion factor hi phase phosphoprotein 2 (MPP2) as an interaction partner of E7 , Specific interaction of the tno proteins both in ratio and in vivo in mam malian cells was detected. The interaction of MPP2 with E7 is functionally relevant since MPP2 enhances the E7/Ha-Ras co-transformation of rat embryo fibroblasts. In addition HPV16 E7, but neither non-transforming mutants of HPV16 E7 nor low risk HPV6 E7, was able to stimulate MPP2-specific transcri ptional activity. Thus, MPP2 is a potentially important target for E7-media ted transformation.