Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm.
Although Daxx (death-associated protein) was first reported to mediate the apoptotic signal from Fas to JNK in the cytoplasm, other data suggested that Daxx is mainly located in the nucleus as a transcriptional regulator. Here, we demonstrated that cellular localization of Daxx could be determined by the relative concentration of a proapoptotic kinase, apoptosis signal-regulating kinase 1 (ASK1) by using immunofluorescence and transcriptional reporter assay. ASK1 sequestered Daxx in the cytoplasm and inhibited the repressive activity of Daxx in transcription. In addition, Daxx was bound to the activated Fas only in the presence of ASK1, accelerating the Fas-mediated apoptosis. These results suggest that Daxx requires ASK1 for its cytoplasmic localization and Fas-mediated signaling. Taken together, we could conclude that ASK1 controls the dual function of Daxx as a transcriptional repressor in the nucleus and as a proapoptotic signal mediator in the cytoplasm.
Ko
Y G
YG
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kang
Y S
YS
Park
H
H
Seol
W
W
Kim
J
J
Kim
T
T
Park
H S
HS
Choi
E J
EJ
Kim
S
S
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D029681:Arabidopsis Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D056970:Co-Repressor Proteins; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010940:Plant Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
C120363:ASK1 protein, Arabidopsis; D048868:Adaptor Proteins, Signal Transducing; D029681:Arabidopsis Proteins; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010940:Plant Proteins; D004247:DNA; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C482858:MAP3K5 protein, human