HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis
- 153 Downloads
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.
KeywordsTax Ras Erk1/2 HTLV-1 GAP1m Apoptosis
We would like to thank Mr. Pierantonio Gallo and Mr. Renzo Grancara for artwork, and Mrs. C. Case for help in preparing the manuscript. This work was supported by grants from European Union (contract no 2005-018704), Associazione Italiana per la Ricerca sul Cancro, Ministero della Salute (progetto RFPS-2006-2-342010). N.V. and R.T. are supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro.
- 6.Grassmann R, Dengler C, Muller-Fleckenstein I et al (1989) Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Proc Natl Acad Sci USA 86:3351–3355. doi:10.1073/pnas.86.9.3351 PubMedCrossRefGoogle Scholar
- 13.Haller K, Wu Y, Derow E, Schmitt I, Jeang KT et al (2002) Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein. Mol Cell Biol 22:3327–3338. doi:10.1128/MCB.22.10.3327-3338.2002 PubMedCrossRefGoogle Scholar
- 52.Kim YM, Ramirez JA, Mick JE (2007) Molecular characterization of the tax-containing HTLV-1 enhancer complex reveals a prominent role for CREB phosphorylation in tax transactivation. J Biol Chem 280:29653–29660Google Scholar