A schizont-derived protein, TpSCOP, is involved in the activation of NF-kappaB in Theileria parva-infected lymphocytes.
Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the nuclear factor-kappa B (NF-kappaB) is activated in schizont-infected cells, making T. parva-transformed cells resistant to apoptosis. However, the mechanism by which the parasite triggers the activation of NF-kappaB remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP (T. parvaschizont-derived cytoskeleton-binding protein), which is expressed in the schizont stage of T. parva. TpSCOP was shown to interact with F-actin in vitro. Expression of TpSCOP in a murine lymphocytic cell line resulted in the activation of NF-kappaB signaling pathways, leading to apoptosis resistance. The activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), was also detected. Furthermore, the introduction of TpSCOP into T. parva-infected cells also enhanced the activation of NF-kappaB. This is the first report to demonstrate that a parasite-derived molecule has the ability to activate the host NF-kappaB pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection.
Hayashida
Kyoko
K
Department of Education and Collaboration, Research Center for Zoonosis Control, Hokkaido University, Kita-20, Nishi-10, Kita-ku, Sapporo, Hokkaido 001-0020, Japan.
Hattori
Masakazu
M
Nakao
Ryo
R
Tanaka
Yoshimasa
Y
Kim
Jung-Yeon
JY
Inoue
Noboru
N
Nene
Vishvanath
V
Sugimoto
Chihiro
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000276:immunology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015800:Protozoan Proteins / Q000276:immunology*; D052939:Schizonts / Q000276:immunology*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D016797:Theileria parva / Q000276:immunology*
D000199:Actins; D016054:DNA, Protozoan; D052002:NF-kappa B p50 Subunit; D015800:Protozoan Proteins; C073701:Nfkb1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases