Elsevier

Neuroscience Letters

Volume 359, Issue 3, 15 April 2004, Pages 155-158
Neuroscience Letters

Proliferation inhibition of astrocytes, neurons, and non-glial cells by intracellularly expressed human immunodeficiency virus type 1 (HIV-1) Tat protein

https://doi.org/10.1016/j.neulet.2004.02.012Get rights and content

Abstract

Human immunodeficiency virus type 1 Tat protein is one of the soluble neurotoxins. Most studies have to date focused on Tat as an extracellular molecule and its role in neuronal apoptosis, as recombinant Tat protein is often used in these studies. In this study, we expressed Tat protein in astrocytes and neurons, and examined its effects on these cells. We found that Tat expression resulted in growth inhibition of astrocytes, neurons, as well as non-glial cells 293T. We further showed that Tat interacted with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA. These data demonstrate that Tat inhibited cell proliferation when expressed intracellularly, and suggest that Tat interactions with multiple cell cycle regulators may account for this anti-proliferative effect. These results support the notion that Tat-induced neuropathogenesis is mediated by multiple mechanisms involving both intracellular and extracellular Tat protein.

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Acknowledgements

This work was supported by grants R01NS39804 and R01MH65158 (to J.J.H.) from the National Institutes of Health.

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