D'Agostino D M, Silic-Benussi M, Hiraragi H, Lairmore M D, Ciminale V
Department of Oncology and Surgical Sciences, University of Padova, Padova 35128, Italy.
Cell Death Differ. 2005 Aug;12 Suppl 1(Suppl 1):905-15. doi: 10.1038/sj.cdd.4401576.
p13(II) of human T-cell leukemia virus type 1 (HTLV-1) is an 87-amino-acid protein that is targeted to the inner mitochondrial membrane. p13(II) alters mitochondrial membrane permeability, producing a rapid, membrane potential-dependent influx of K(+). These changes result in increased mitochondrial matrix volume and fragmentation and may lead to depolarization and alterations in mitochondrial Ca(2+) uptake/retention capacity. At the cellular level, p13(II) has been found to interfere with cell proliferation and transformation and to promote apoptosis induced by ceramide and Fas ligand. Assays carried out in T cells (the major targets of HTLV-1 infection in vivo) demonstrate that p13(II)-mediated sensitization to Fas ligand-induced apoptosis can be blocked by an inhibitor of Ras farnesylation, thus implicating Ras signaling as a downstream target of p13(II) function.
人类嗜T淋巴细胞病毒1型(HTLV-1)的p13(II)是一种由87个氨基酸组成的蛋白质,定位于线粒体内膜。p13(II)会改变线粒体膜通透性,导致钾离子(K(+))快速、依赖膜电位的内流。这些变化会使线粒体基质体积增加并碎片化,可能导致去极化以及线粒体钙离子摄取/保留能力的改变。在细胞水平上,已发现p13(II)会干扰细胞增殖和转化,并促进神经酰胺和Fas配体诱导的细胞凋亡。在T细胞(HTLV-1体内感染的主要靶细胞)中进行的实验表明,法尼基化Ras抑制剂可阻断p13(II)介导的对Fas配体诱导凋亡的敏感性,因此表明Ras信号传导是p13(II)功能的下游靶点。