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Titolo:
RAF-1 KINASE TARGETS GA-BINDING PROTEIN IN TRANSCRIPTIONAL REGULATIONOF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROMOTER
Autore:
FLORY E; HOFFMEYER A; SMOLA U; RAPP UR; BRUDER JT;
Indirizzi:
UNIV WURZBURG,INST RADIOBIOL & CELL RES D-97078 WURZBURG GERMANY UNIV WURZBURG,INST RADIOBIOL & CELL RES D-97078 WURZBURG GERMANY NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB FREDERICK MD 21702
Titolo Testata:
Journal of virology
fascicolo: 4, volume: 70, anno: 1996,
pagine: 2260 - 2268
SICI:
0022-538X(1996)70:4<2260:RKTGPI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
SERUM RESPONSE ELEMENT; LONG TERMINAL REPEAT; KAPPA-B SITE; GENE-EXPRESSION; DNA-BINDING; REQUIRES RAF-1; FACTOR EF-1A; C-FOS; ACTIVATION; ENHANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
E. Flory et al., "RAF-1 KINASE TARGETS GA-BINDING PROTEIN IN TRANSCRIPTIONAL REGULATIONOF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROMOTER", Journal of virology, 70(4), 1996, pp. 2260-2268

Abstract

The serine/threonine protein kinase Raf-1 is a component of a conserved intracellular signaling cascade that controls responses to various extracellular stimuli. Transcription from several promoters, includingthe oncogene-responsive element in the polyomavirus enhancer, the c-fos promoter, as well as other AP-1- and Ets-dependent promoters, can be induced by Raf-1 kinase. Previously, we have shown that activated Raf-1 kinase transactivates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and have identified the NF-kappa B binding motif as a Raf-1-responsive element (RafRE). We now report that Raf-1 kinase-induced transactivation from the HIV RafRE involves the purine-rich-repeat-binding protein (GABP), which is composed of two distinct subunits (alpha and beta). GABP alpha is an Ets oncogene-related DNA-binding protein, and GABP beta contains four ankyrin-like repeats that have been shown to be essential in protein-protein interactions. In electrophoretic mobility shift assays using nuclear extracts from human Jurkat T cells, a protein-DNA complex which was supershifted with antiserum against GABP alpha and GABP beta was observed. Purified recombinant GABP alpha and beta interact with the HIV RafRE as judged from DNA binding assays. Cotransfection experiments with GABP alpha and beta andRaf-1 kinase demonstrate synergistic transactivation of the HIV-1 promoter. Point mutations in the HIV RafRE abolished the Raf-1 kinase- aswell as GABP alpha- and beta-induced transactivation. The observed Raf-1-GABP synergism presumably involves phosphorylation of GABP subunits, as treatment of cells with Raf-1 kinase activators serum and 12-O-tetradecanoylphorbol-13-acetate increases phosphorylation of GABP in vivo. However, GABP is not a target of Raf-1 kinase, instead, it is a substrate of mitogen-activated protein kinase (MAPK/ERK), since in vitrophosphorylation of GABP alpha and beta was achieved by the reconstituted protein kinase cascade but not with purified Raf-1 or MEK. These results suggest that Raf-1 kinase-induced activation of the HIV-1 promoter is mediated by the classical cytoplasmic cascade resulting in MAPK/ERK-mediated phosphorylation of GABP alpha and beta. Because the HIV RafRE corresponds to a region within the promoter which is essential for regulation of HIV-1 expression, the data indicate that in addition to NF-kappa B, GABP transcription factors are important for induced expression of HIV.

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Documento generato il 20/09/20 alle ore 10:03:14