Polyomavirus small T antigen transactivates genes by its ability to provoke the synthesis and the stabilization of MYC.
DNA tumor viruses are capable of driving quiescent cells into the cell cycle. In case of polyomaviridae, two viral proteins, the large and the small (ST) T antigens are responsible for this outcome. ST interacts with the protein phosphatase PP2A and with chaperons of the dnaK type and leads to the transactivation of several genes, which play a role in S-phase induction. One of these is the transcription factor myelocytomatosis (MYC), which by itself is an important regulator of growth. Microarray analysis has revealed several ST-induced genes, which are also targets of MYC; hence, ST may induce these genes via MYC. Experiments shown here are in line with this assumption. MYC-regulated genes are induced by ST at later times than MYC and a MYC responsive promoter is stimulated by ST. Regulation of MYC occurs through signal transduction pathways, which are co-ordinated by PP2A suggesting that they may be targets of ST. Here, we show that this is the case as important kinases involved in these pathways appear in the active phosphorylated form in the presence of ST. Inhibition of these kinases interferes with MYC induction and inhibition of MYC activity blocks ST-mediated transactivation.
Klucky
B
B
Division of Molecular Biology, Department of Medical Biochemistry, MFPL, Medical University of Vienna, Vienna, Austria.
Wintersberger
E
E
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases