Model of RNF4-mediated Tax relocalization. The HTLV1 Tax protein can sequester DNA-repair proteins (eg, DNA-PK and Chk2) into TSS's and also transactivate the promoters of host genes (eg, those responsive to CREB, AP-1, or p300/CBP). Tax enters the nucleus as a multimer, coincident with sumoylation, and forms TSS. After DNA damage, RNF4 targets sumoylated Tax for ubiquitylation resulting in nuclear egress of Tax. In the cytoplasm, interactions between Tax and NEMO lead to activation of the NF-κB pathway. Our work shows that this virus has adopted a sophisticated anti-apoptotic approach that depends on the STUbL RNF4.