Functional and Physical Consequence of Human Immunodefficiency Virus Transactivator TAT Interaction with Human Cell Cycle Regulator p53

Human immunodeficiency virus (HIV) transactivator Tat is a potent activator of both viral and cellular genes. Tat has also been implicated in the development of AIDS-related malignancy. Here, we show that Tat physically and functionally is able to sequester the cell cycle check point protein p53. This sequestration results in non-functional promoter activity of cyclin-dependent kinase/cyclin inhibitor, namely p21 (Waf1). Therefore, it is proposed that a Tat/p53 complex in vivo may deregulate p53 responsive genes, hence allowing for deregulation of check point, which may lead to development of malignancies.