Schematic view of the Tax/p53/Wip1/MDM2/ARF interplay. Double strands breaks (DSB) induced by Tax-driven genomic stress are frequent in ATL cells. Recognition of these DSB by γH2AX initiates the DNA damage response (DDR) and signals to the p53 tumor suppressor that arrests the cell cycle, allows DNA repair, and induces apoptosis or senescence. p53 activity is controlled by MDM2/ARF and Wip1. MDM2 is an E3 ubiquitin ligase that degrades p53 and is a first arm of a p53-negative feedback loop. The second mechanism is created by Wip1 that inhibits the DDR through dephosphorylation of ATM Ser1981 and CHK2 Thr68.