Apoptosis Signal-regulating Kinase 1 Controls the Proapoptotic Function of Death-associated Protein (Daxx) in the Cytoplasm

Young Gyu Ko, Young Sun Kang, Heonyong Park, Wongi Seol, Jinyoung Kim, Taeho Kim, Hee Sae Park, Eui Ju Choi, Sunghoon Kim

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)39103-39106
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number42
DOIs
Publication statusPublished - 2001 Oct 19

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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