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Daxx, a novel Fas-binding protein that activates JNK and apoptosis

X Yang1, R Khosravi-Far, H Y Chang

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.

Cell
|June 27, 1997
PubMed

Insights

Researchers discovered Daxx, a protein that enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. Daxx defines a distinct apoptotic pathway downstream of Fas, working alongside the FADD pathway.

Area of Science:

  • Cell biology
  • Molecular biology
  • Immunology

Background:

  • The Fas receptor is a key mediator of programmed cell death (apoptosis).
  • Understanding the signaling pathways downstream of Fas is crucial for controlling cell death.
  • The Fas death domain is critical for initiating apoptotic signaling.

Purpose of the Study:

  • To identify novel proteins involved in Fas-mediated apoptosis.
  • To elucidate the role of the newly identified protein, Daxx, in apoptosis.
  • To characterize the signaling pathways regulated by Daxx downstream of Fas.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • Overexpression studies to evaluate functional effects.
  • Analysis of apoptosis and Jun N-terminal kinase (JNK) pathway activation.
  • Dominant-negative inhibition assays.

Main Results:

  • Daxx specifically binds to the Fas death domain.
  • Overexpression of Daxx enhances Fas-induced apoptosis and JNK activation.
  • A distinct region of Daxx activates JNK and apoptosis, while its Fas-binding domain inhibits these processes.
  • The Daxx apoptotic pathway is modulated by Bcl-2 and JNK pathway components.
  • Daxx and FADD represent two separate apoptotic pathways downstream of Fas.

Conclusions:

  • Daxx is a novel signaling protein that plays a significant role in Fas-mediated apoptosis.
  • Daxx activates the JNK pathway and defines a distinct apoptotic signaling cascade.
  • The interplay between Daxx and FADD pathways provides a more comprehensive understanding of Fas signaling.

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