Clarification of mechanism of HTLV-1 Tax protein on cell immortalization.

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Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent for the development of adult T-cell leukemia (ATL). Tax encoded by HTLV-1 plays important role in immortalization of primary human lymphocytes. This study aimed to clarify what roles of Tax was involved in the mechanism of immortalization of cells. We found that Tax interacted with not only co-activator but also co-repressor of transcription. The interaction of Tax with co-activator CBP resulted in suppression of p53 of Tax producing cells. Moreover, we found that p73, a p53 family protein was also trans-suppressed by Tax. Apart from regulation of transcription, Tax is known to regulate cell cycle by interacting or suppressing function of cell cycle inhibitors. P21, one of cycline inhibitors is over-expressed in Tax expressing cells. MT-2 cells which expresses high level of p21 is not arrested at G1. p21 inhibits cell cycle progression by G1 arrest when transiently expressed in COS cells. Co-production of Tax and p21 in COS cells did not sequestered the cell cycle arrest. Thus it is suggested that unidentified mechanism is involved in sequesterthe function of p21 in HTLV-1 infected cells. Clarification of such the mechanism may help to understand Tax dependent immortalization of cells.