Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3.
Daxx has been shown to play an essential in type I interferon (IFN-alpha/beta)-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and nuclear translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify the mechanism of Daxx-mediated apoptosis signaling in B lymphocyte progenitors, here we introduced an efficient suicide switch in a murine pro-B cell line, BAF3, by expressing FK506-binding protein-fused Fas intracellular domain (FKBP-Fas) and Daxx. It allows us to monitor Fas/Daxx-mediated signal by induction of Fas dimerization with the dimerizer drug AP20187. AP20187-mediated Fas dimerization induced not only apoptosis but also Jun N-terminal kinase (JNK) activation. However, AP20187 had no effect on cells expressing either Fas or Daxx only. Furthermore, expression of a JNK inhibitor, the JNK-binding domain of JIP-1, resulted in resistance to AP20187-mediated apoptosis in cells expressing FKBP-Fas and Daxx. These results imply that our novel suicide switch system may provide a powerful tool to delineate or identify the signaling molecules for Daxx-mediated apoptotic machinery in B lymphocyte progenitors through JNK activation.
Muromoto
Ryuta
R
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Yamamoto
Tetsuya
T
Yumioka
Taro
T
Sekine
Yuichi
Y
Sugiyama
Kenji
K
Shimoda
Kazuya
K
Oritani
Kenji
K
Matsuda
Tadashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D002352:Carrier Proteins / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D056970:Co-Repressor Proteins; D004789:Enzyme Activation; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000502:physiology*; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology*
C463061:AP20187; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D016559:Tacrolimus