HIV-1-Tat protein activates phosphatidylinositol 3-kinase/AKT-dependent survival pathways in Kaposi's sarcoma cells

Maria Chiara Deregibus, Vincenzo Cantaluppi, Sophie Doublier, Maria Felice Brizzi, Ilaria Deambrosis, Adriana Albini, Giovanni Camussi

Research output: Contribution to journalArticle

Abstract

In this study we found that Tat protected vincristine-treated Kaposi's sarcoma cells from apoptosis and from down-regulation of several anti-apoptotic genes such as AKT-1, AKT-2, BCL2, BCL-XL, and insulin-like growth factor I and induced the de novo expression of the interleukin-3 gene. Moreover, we found that Tat enhanced phosphorylation of AKT and BAD proteins. The inhibition of phosphatidylinositol 3-kinase with two unrelated pharmacological inhibitors, wortmannin and LY294002, abrogated both the anti-apoptotic effect and the phosphorylation of AKT induced by Tat. After treatment with Tat, the AKT enzymatic activity showed a biphasic increase: an early activation (15 min), independent from protein synthesis; and a delayed activation (24 h), which was significantly decreased upon blockage of protein synthesis. Experiments with a function blocking antivascular endothelial cell growth factor receptor-2 antibody suggested that both the early and delayed AKT activation and the protection from apoptosis were triggered by the interaction of Tat with vascular endothelial cell growth factor receptor-2. Moreover, experiments with function-blocking antibodies directed against insulin-like growth factor I/insulin-like growth factor I receptor or interleukin-3 indicated their involvement in the delayed activation of AKT and their contribution to the anti-apoptotic effect of Tat on vincristine-treated Kaposi's sarcoma cells.

Original languageEnglish
Pages (from-to)25195-25202
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number28
DOIs
Publication statusPublished - Jul 12 2002

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Human Immunodeficiency Virus tat Gene Products
Phosphatidylinositol 3-Kinase
tat Gene Products
Kaposi's Sarcoma
HIV-1
Vascular Endothelial Growth Factor Receptor
Interleukin-3
Chemical activation
Vincristine
Insulin-Like Growth Factor I
Phosphorylation
Apoptosis
Vascular Endothelial Growth Factor Receptor-2
IGF Type 1 Receptor
Proteins
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Blocking Antibodies
Genes
Growth Factor Receptors
Endothelial cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

HIV-1-Tat protein activates phosphatidylinositol 3-kinase/AKT-dependent survival pathways in Kaposi's sarcoma cells. / Deregibus, Maria Chiara; Cantaluppi, Vincenzo; Doublier, Sophie; Brizzi, Maria Felice; Deambrosis, Ilaria; Albini, Adriana; Camussi, Giovanni.

In: Journal of Biological Chemistry, Vol. 277, No. 28, 12.07.2002, p. 25195-25202.

Research output: Contribution to journalArticle

Deregibus, Maria Chiara ; Cantaluppi, Vincenzo ; Doublier, Sophie ; Brizzi, Maria Felice ; Deambrosis, Ilaria ; Albini, Adriana ; Camussi, Giovanni. / HIV-1-Tat protein activates phosphatidylinositol 3-kinase/AKT-dependent survival pathways in Kaposi's sarcoma cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 28. pp. 25195-25202.
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