Specific control of cell cycle entry by tyrosine phosphorylation of Cdk4

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In higher eukaryote, a majority of cells are arrested in a quiescent state. The G0-G1 transition is important because G0 arrested cells must enter G1 phase of the cell cycle when they work. Recently we Rreported That Cdk4 is inactivated by phosphorylation on tyrosine 17 and that this inactivation is required for UV irradiation induced G1 checkpoint arrest. Here we show that this Cdk4 phosphorylation occurs only in a quiescent state and dephosphorylation during their cell cycle entry. In the cells traversing G1, Cdk4 is not tyrosine-phosphorylated. Ultraviolet irradiation blocks dephosphorylation, thereby preventing the "start" of the cell cycle. Exponentially growing cells are not able to arrestin G1 upon UV irradiation, because Cdk4 is not phosphory lated. We conclude that tyrosine phosphorylation of Cdk4 is specifically used for the control of the G0-G1 transition and constitutes a major DNA damage-responsive checkpoint mechanism during this transition.