Differential phosphorylation of the HPV-16 E7 oncoprotein during the cell cycle

The human papillomavirus type 16 encodes two principal oncoproteins, E6 and E7, The E7 protein has bean shown to deregulate the cell cycle through int eractions with a variety of proteins involved in cell cycle control and tra nscriptional regulation. These activities result in E7 being able to cooper ate with activated oncogenes in the transformation of primary rodent cells, and with the viral E6 protein during human keratinocyte immortalization. A lthough a large number of activities have been ascribed to the E7 protein, little is known about its regulation during the cell cycle. We have perform ed a series of studies to investigate potential changes in E7 phosphorylati on during the cell cycle and we show that E7 is indeed differentially phosp horylated. Casein kinase II is the principal kinase during the early part o f the cell cycle, but this activity decreases rapidly as cells progress tow ard S phase. In addition, E7 is transiently phosphorylated at Ser71 in S ph ase by another, as yet unknown, kinase. These results demonstrate different ial regulation of the E7 protein during the cell cycle that most likely rep resents a means of providing specificity to E7's activities. (C) 2000 Acade mic Press.