Interaction between HIV-1 Tat and pRb2/p130: a possible mechanism in the pathogenesis of AIDS-related neoplasms.

Tat protein is an early nonstructural protein necessary for virus replication, which is secreted by infected cells and taken up by uninfected cells. Extensive evidence indicates that Tat may be a cofactor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Among these genes, it has recently been shown that pRb2/p130 oncosuppressor protein is one of the targets in the interaction between HIV gene product Tat and host proteins. However, whether the HIV-1 gene product Tat may inactivate the oncosuppressive function of pRb2/p130 has not yet been elucidated. Here, we show that mRNA levels of pRb2/p130 increase in the presence of Tat, whereas no change in the phosphorylation status of pRb2/p130 is observed. In addition, Tat can inhibit the growth control activity exerted by pRb2/p130 in the T98G cell line. Finally, Tat does not compete with E2F-4 in binding to pRb2/p130. The interaction between Tat and pRb2/p130 seems to result in the deregulation of the control exerted by pRb2/p130 on the cell cycle. Taken together, these results open a window on the role of pRb2/p130 in AIDS-related oncogenesis