STAT3 and its phosphorylation are involved in HIV-1 tat-induced transactivation of glial fibrillary acidic protein

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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.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalCurrent HIV Research
Volume13
Issue number1
DOIs
StatePublished - 1 Jan 2015

Fingerprint

STAT3 Transcription Factor
Glial Fibrillary Acidic Protein
Transcriptional Activation
HIV-1
Phosphorylation
Early Growth Response Protein 1
Astrocytes
HIV
tat Gene Products
Proteins
Gliosis
Central Nervous System

Keywords

  • Astrocytes
  • Egr-1
  • GFAP
  • HIV-1 Tat
  • P300
  • STAT3

Cite this

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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.",
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STAT3 and its phosphorylation are involved in HIV-1 tat-induced transactivation of glial fibrillary acidic protein. / Fan, Yan; Timani, Khalid A.; He, Johnny Jianglin.

In: Current HIV Research, Vol. 13, No. 1, 01.01.2015, p. 55-63.

Research output: Contribution to journalArticleResearchpeer-review

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AB - 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.

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