HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis.
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.
Vajente
Nicola
N
Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, via Gattamelata 64, 35128 Padova, Italy.
Trevisan
Roberta
R
Saggioro
Daniela
D
D017209:Apoptosis / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D054876:Prenylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D050505:Mutant Proteins; D011106:Polyisoprenyl Phosphates; D047428:Protein Kinase Inhibitors; C102193:RASA2 protein, human; D051028:bcl-2-Associated X Protein; D020703:ras GTPase-Activating Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); C002963:geranylgeranyl pyrophosphate