Abstract
Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) plays a critical role in HTLV-I-correlated diseases through its ability to deregulate the expression of a vast array of cellular genes. We have previously shown that Tax counteracts apoptosis induced by stimuli triggering mitochondria apoptotic pathway, most likely by activating CREB-mediated transcription and affecting the phosphorylation levels of CREB at Ser-133. Here, we report data that indicate the oncoprotein Ras as a possible mediator of Tax-induced apoptosis protection and suggest a possible role of Tax in Ras activation. In addition, using inhibitors of down stream effectors of Ras, we found that ERK signaling is the most relevant for Tax-mediated apoptosis protection. As a whole, our findings provide intriguing evidence of a possible link between Ras signaling and Tax capability to counteract apoptosis and to enhance P-CREB levels, and implicates a potential role for Ras in HTLV-1-induced diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis* / drug effects
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cytoprotection* / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Products, tax / metabolism*
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HeLa Cells
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Human T-lymphotropic virus 1 / metabolism*
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Humans
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Immunoprecipitation
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MAP Kinase Signaling System / drug effects
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Mutant Proteins / metabolism
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Phosphorylation / drug effects
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Polyisoprenyl Phosphates / pharmacology
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Prenylation / drug effects
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Protein Binding / drug effects
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins p21(ras) / metabolism*
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Response Elements / genetics
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Transcription, Genetic / drug effects
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Transfection
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bcl-2-Associated X Protein / metabolism
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ras GTPase-Activating Proteins / metabolism
Substances
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Cyclic AMP Response Element-Binding Protein
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Gene Products, tax
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Mutant Proteins
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Polyisoprenyl Phosphates
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Protein Kinase Inhibitors
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RASA2 protein, human
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bcl-2-Associated X Protein
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ras GTPase-Activating Proteins
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Extracellular Signal-Regulated MAP Kinases
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)
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geranylgeranyl pyrophosphate