Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3

FEBS Lett. 2003 Apr 10;540(1-3):223-8. doi: 10.1016/s0014-5793(03)00269-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology
  • Carrier Proteins / physiology*
  • Caspases / metabolism
  • Cell Line
  • Co-Repressor Proteins
  • Enzyme Activation
  • Intracellular Signaling Peptides and Proteins*
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Chaperones
  • Nuclear Proteins / physiology*
  • Tacrolimus / analogs & derivatives*
  • Tacrolimus / pharmacology
  • fas Receptor / physiology*


  • AP20187
  • Carrier Proteins
  • Co-Repressor Proteins
  • Daxx protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Nuclear Proteins
  • fas Receptor
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Caspases
  • Tacrolimus