Vajente Nicola, Trevisan Roberta, Saggioro Daniela
Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, via Gattamelata 64, 35128 Padova, Italy.
Apoptosis. 2009 Feb;14(2):153-63. doi: 10.1007/s10495-008-0289-3.
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.
人类T细胞白血病病毒1型（HTLV-1）的Tax蛋白通过其失调大量细胞基因表达的能力，在与HTLV-1相关的疾病中发挥关键作用。我们之前已经表明，Tax可对抗由触发线粒体凋亡途径的刺激所诱导的细胞凋亡，最有可能是通过激活CREB介导的转录并影响CREB在Ser-133位点的磷酸化水平来实现的。在此，我们报告的数据表明癌蛋白Ras可能是Tax诱导的细胞凋亡保护的介质，并提示Tax在Ras激活中可能发挥的作用。此外，使用Ras下游效应器的抑制剂，我们发现ERK信号传导与Tax介导的细胞凋亡保护最为相关。总体而言，我们的研究结果提供了有趣的证据，表明Ras信号传导与Tax对抗细胞凋亡和提高P-CREB水平的能力之间可能存在联系，并暗示Ras在HTLV-1诱导的疾病中可能发挥的作用。
