STAT3 and Its Phosphorylation are Involved in HIV-1 Tat-Induced Transactivation of Glial Fibrillary Acidic Protein

Author(s): Yan Fan, Khalid Amine Timani, Johnny J. He

Journal Name: Current HIV Research

Volume 13 , Issue 1 , 2015

Become EABM
Become Reviewer

Abstract:

Human immunodeficiency virus type 1 (HIV-1) Tat protein is a major pathogenic factor in HIV-associated neurological diseases; it exhibits direct neurotoxicity and indirect astrocyte-mediated neurotoxicity. We have shown that Tat alone is capable of activating glial fibrillary acidic protein (GFAP) expression and inducing astrocytosis involving sequential activation of early growth response protein 1 (Egr-1) and p300. In this study, we determined the roles of signal transducer and activator of transcription 3 (STAT3) in Tat-induced GFAP transactivation. STAT3 expression and phosphorylation led to significant increases in GFAP transcription and protein expression. Tat expression was associated with increased STAT3 expression and phosphorylation in Tat-expressing astrocytes and HIV-infected astrocytes. GFAP, Egr-1 and p300 transcription and protein expression all showed positive response to STAT3 and its phosphorylation. Importantly, knockdown of STAT3 resulted in significant decreases in Tat-induced GFAP and Egr-1 transcription and protein expression. Taken together, these findings show that STAT3 is involved in and acts upstream of Egr1 and p300 in the Tat-induced GFAP transactivation cascade and suggest important roles of STAT3 in controlling astrocyte proliferation and activation in the HIV-infected central nervous system.

Keywords: Astrocytes, HIV-1 Tat, Egr-1, p300, GFAP, STAT3.

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 13
ISSUE: 1
Year: 2015
Page: [55 - 63]
Pages: 9
DOI: 10.2174/1570162X13666150121115804

Article Metrics

PDF: 41
HTML: 1