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Lüscher-Firzlaff, JM, Westendorf, JM, Zwicker, J, Burkhardt, H, Henriksson, M, Müller, R, Pirollet, F and Lüscher, B (1999) Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation. Oncogene 18:5620-30


The high risk human papillomavirus (HPV) type 16 E7 protein affects cell growth control and promotes transformation by interfering with functions of cellular proteins. A key target of E7 is the tumor suppressor protein p105RB. Although this interaction is required for E7-dependent transformation, other cellular molecules must also be involved, because some E7 mutants that have reduced transforming abilities still bind to p105RB. In order to identify 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 transcription factor M phase phosphoprotein 2 (MPP2) as an interaction partner of E7. Specific interaction of the two proteins both in vitro and in vivo in mammalian 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 transcriptional activity. Thus, MPP2 is a potentially important target for E7-mediated transformation.


PubMed Online version:10.1038/sj.onc.1202967


Animals; Bacterial Proteins/genetics; Bacterial Proteins/physiology; COS Cells; Cell Transformation, Viral; Cells, Cultured; Cercopithecus aethiops; DNA, Complementary/genetics; Fibroblasts/cytology; Forkhead Transcription Factors; Genes, ras; Humans; Mice; Oncogene Proteins, Viral/metabolism; Papillomaviridae/physiology; Papillomavirus E7 Proteins; Phosphoproteins/chemistry; Phosphoproteins/metabolism; Protein Binding; Protein Conformation; Proto-Oncogene Proteins p21(ras)/physiology; Rabbits; Rats; Recombinant Fusion Proteins/metabolism; Retinoblastoma Protein/metabolism; Serine Endopeptidases/genetics; Serine Endopeptidases/physiology; Trans-Activators/metabolism; Transcription Factors; Transcriptional Activation/physiology; Two-Hybrid System Techniques



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

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