c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

Oncogene (2005) 24, 1075–1083

Speaker : 余婧萱                                Time : 13:00~14:00  3/8/2006

Commentator : 劉校生  老師                      Place: Room 601

Abstract:

Theileria is an obligate intracellular protozoan parasite. Theileria infection cause bovine lymphocyte transformation. This state can be reserved by killing the parasite with a specific drug BW 720c. The lymphocytes would be dead by apoptosis rapidly when the parasites were killed. c-myc is an oncogene which plays an important role of cell transformation and STAT3 is one of the transcription activators of c-myc. In Theileria infected B cell, both of the phosphorylation STAT3 and c-myc were increased. That is one way to keep the host proliferation and also to help the proliferation of the infected parasite. When the Thelileria infected, the c-myc gene was constitutively activated and stabilized by the CK2 expression. This result can prevent the c-myc degradation by the proteasome activity. JAK2 play an important role in the singling from STAT3 to c-myc. JAK2 was inhibited by the AG490 during the protozoa infected, the phosphorylation of STAT3 and c-myc were both reduced. Transfected the inactivated mutant of JAK2 and STAT3 into the infected cell, c-myc expression was less than the untransfected one, in respectively. The infected cell can be rescued by the transfection of c-myc, during the JAK2 inhibitor treated. This notion JAK2/STAT3 signaling pathway was contributed to the c-myc activation. When JAK2/STAT3 pathway was inhibited, the caspase-depended apoptosis was occurred in the infected cell. That means the anti-apoptosis was regulated way by the JAK2/STAT3 singling in the Theilrea infection. The c-myc expression can be induced by the supplement of GM-CSF in the infected B cell in vitro, which means the GM-CSF autocrine loop in part mediate the c-myc transcription induced by Theileria infection. Therefore, Theileria ensure the survival of host lymphocyte via specific activation of c-myc.

References:

1. F. Dessauge, R. Lizundia, M. Baumgartner, M. Chaussepied and G. Langsley Taking the Myc is bad for Theileria TRENDS in Parasitology.8, 377-385 (2005)

2. F. Dessauge, R. Lizundia and G. Langsley Constitutively activated CK2 potentially plays a pivotal role in Theileria- induced lymphocyte transformation Parasitology 130, S37-S44 (2005)