Tax protein of HTLV-1 inhibits CBP/p300-mediated transcription by interfering with recruitment of CBP/p300 onto DNA element of E-box or p53 binding site

Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a potent tran scriptional regulator which can activate or repress specific cellular genes and has been proposed to contribute to leukemogenic processes in adult T-c ell leukemia, The molecular mechanism of Tax-mediated trans-activation has been well investigated. However, trans-repression by Tax remains to be stud ied in detail, although it is known to require a specific DIVA element such as E-box or p53 binding site. Examining possible mechanisms of trans-repre ssion, we found that co-expression of E47 and p300 activated E-box dependen t transcription and this activation was efficiently repressed by Tax. In th is system, Tax bound to p300 and decreased the level of p300 complexed on t he E-box element. Similarly, Tax inhibited transcription directed by p53 an d CBP, reducing the level of CBP on the p53 binding site. These results ind icate that Tax interferes with recruitment of CBP/p300 into protein complex es on E-box and p53 binding site through its binding to CBP/p300. In contra st to these findings, we observed that Tax increased the level of CBP on th e viral 21-bp enhancer which is trans-activated by Tax. From these observat ions, we propose a universal mechanism for Tax-mediated trans-repression an d trans-activation of transcription in which Tax binds to CBP/p300 and dete rmines the accessibility of CBP/p300 to protein complexes on specific DNA e lement.