title: STAT3 and its phosphorylation are involved in HIV-1 Tat-induced transactivation of glial fibrillary acidic protein.
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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.forename: Khalid Amine
authors.initials: KA
authors.lastname: Timani
authors.affiliation: Department of Cell Biology and Immunology, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA. johnny.he@unthsc.edu.
authors.forename: Johnny J
authors.initials: JJ
authors.lastname: He
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus