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

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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.

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Acknowledgements

We thank Professor Cosima Baldari, Department of Evolutionary Biology of the University of Siena, for her critical review of the manuscript. This work is supported by grants from CNR and MURST-LAG-CO3 (CC), NIH (R21-CA099955), and Sbarro Health Research Organization (AG), short-term mobility 2001 from CNR, and ‘Progetto Giovani Ricercatori’, University of Siena (GDF).

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Authors and Affiliations

  1. Department of Human Pathology and Oncology, University of Siena, Siena, Italy

    Giulia De Falco, Cristiana Bellan, Stefano Lazzi, Domenico La Sala, Piero Tosi & Lorenzo Leoncini

  2. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science & Technology, Temple University, Philadelphia, 19122, PA, USA

    Giulia De Falco, PierPaolo Claudio, Caterina Cinti & Antonio Giordano

  3. ITOI-CNR, Bologna unit, Bologna, Italy

    Domenico La Sala & Caterina Cinti

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  1. Giulia De Falco
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  2. Cristiana Bellan
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  3. Stefano Lazzi
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  4. PierPaolo Claudio
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  5. Domenico La Sala
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  7. Piero Tosi
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  8. Antonio Giordano
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  9. Lorenzo Leoncini
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Correspondence to Antonio Giordano.

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De Falco, G., Bellan, C., Lazzi, S. et al. Interaction between HIV-1 Tat and pRb2/p130: a possible mechanism in the pathogenesis of AIDS-related neoplasms. Oncogene 22, 6214–6219 (2003). https://doi.org/10.1038/sj.onc.1206637

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  • DOI: https://doi.org/10.1038/sj.onc.1206637

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