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

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

De Falco G,Bellan C,Lazzi S,Claudio P,La Sala D,Cinti C,Tosi P,Giordano A,Leoncini L

doi

10.1038/sj.onc.1206637

subject

Has Abstract

pub_date

2003-09-18 00:00:00

pages

6214-9

issue

40

eissn

0950-9232

issn

1476-5594

pii

1206637

journal_volume

22

pub_type

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