U5 region of the human immunodeficiency virus type 1 long terminal repeat contains TRE-like cAMP-responsive elements that bind both AP-1 and CREB/ATF proteins.
Virology
; 233(1): 235-45, 1997 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-9201233
ABSTRACT
Activating protein-1 (AP-1) binding phorbol ester responsive elements (TRE) are located downstream of the transcription initiation site in the U5 region of the human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR). These downstream sequence elements, termed DSE, can bind cFos and junD and transmit protein kinase C (PKC) activation signals to the LTR. Further studies suggested the DSE might also bind AP-1-related proteins of the CREB/ATF family. Since enhanced HIV-1 expression is associated with activation of the cAMP-dependent protein kinase A (PKA) signaling pathway, we determined whether binding of CREB/ATF proteins to the DSE mediate cAMP/PKA activation of the HIV-1 LTR. In the present study. DSE binding complexes in nuclear protein extracta from colonic epithelial cells are shown to contain ATF-1, ATF-2, and CREB and transfection of either an ATF-2 or PKA expressing plasmid transactivated the DSE. Cholera toxin (Ctx), a potent activator of the cAMP/PKA pathway. Increased HIV-1 virus production from a latently infected promonocytic cell line, U1. Ctx increased LTR promoter activity and increased the CREB content of DSE binding complexes. Transfection of U1 cells with a series of mutant LTR reporter constructs demonstrated that the Ctx response was in large part mediated by the DSE. The Ctx response was also mediated by a heterologous promoter containing multiple TRE sites. Nuclear protein extracts from a T-cell line infected by HIV-1 contained higher levels of CREB/ATF proteins and manifested increased CREB/ATF binding activity. Collectively, these results indicate the DSE are TRE-like cAMP responsive elements that bind both AP-1 and CREB/ATF permitting induction of the HIV-1 LTR by both PKC and PKA activation signals.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Repetição Terminal Longa de HIV
/
HIV-1
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Fator de Transcrição AP-1
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Proteínas de Ligação a DNA
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article