The human T-cell leukemia virus type 1 p13II protein: effects on mitochondrial function and cell growth

• Published in: Cell death and differentiation Vol. 12 Suppl 1; no. S1; pp. 905 - 915
• Main Authors: D'Agostino, D M, Silic-Benussi, M, Hiraragi, H, Lairmore, M D, Ciminale, V
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2005
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Apoptosis - drug effects; Calcium - metabolism; Cell death; Cell Death - drug effects; Cell growth; Cell Proliferation - drug effects; Cloning; Cloning, Molecular; Cytokines; Genomes; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - metabolism; Humans; Infections; Intracellular Membranes - drug effects; Leukemia; Ligands; Lymphocytes; Lymphoma; Mitochondria - drug effects; Mitochondria - physiology; Molecular Sequence Data; Oncology; Permeability; Proteins; Retroviridae Proteins - biosynthesis; Retroviridae Proteins - genetics; Retroviridae Proteins - pharmacology; Signal transduction; Signal Transduction - drug effects; Veterinary medicine; Viruses
• ISSN: 1350-9047; 1476-5403
• 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.