Tax immortalizes T lymphocytes and induces leukemia in transgenic mice.148,149 It promotes viral transcription from a promoter located within the long terminal repeat (LTR).150,151,152 The N-terminus of Tax (Figure 4A) directly binds to CREB to form a ternary complex of TRE–Tax–CREB (Tax-responsive element–Tax–CREB) within the viral promoter.154,155 Binding of Tax to CREB enhances CREB homodimerization, which strengthens its association with promoter DNA.156 TRE activation requires Tax homodimerization, which involves CREB homodimerization. This evidence concerns the gene CNTN2 and leukemia.