VIRAL ONCOGENESIS AND CELL-CYCLE CONTROL

Increasing evidence suggests a critical role for cell cycle regulatory genes in tumorigenesis in mammals, and oncogenic viruses account for a considerable proportion of cancers in humans. In most cases, infecti on by oncogenic viruses is insufficient for malignant transformation; rather, the viruses provide host cells with additional growth stimuli, which extend the proliferative capacity of the infected cell. This im plies that viral oncogenes can override cellular control mechanisms, w hich in untransformed cells regulate cell cycle progression in respons e to various antiproliferative signals. Recent progress has enabled th e definition of several mammalian cell cycle regulatory genes as targe ts for viral oncoproteins. This new field of investigation was the cen tral topic of a meeting (Viral Oncogenesis and Cell Cycle Control) hel d in Heidelberg in October 1995. In the following, major findings pres ented at this meeting will be summarized. The first part of the meetin g was dedicated to the analysis of cell cycle regulation in normal unt ransformed mammalian cells, followed by an analysis of the interaction of tumor virus oncoproteins with mammalian cell cycle regulators. The latter interactions fall into three categories: viral oncoproteins we re shown to interfere with various signal transduction pathways, to in activate growth-suppressive nuclear proteins by direct binding, and to modulate the expression of key cell cycle regulatory genes.