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Emerging roles for the death adaptor FADD in death receptor avidity and cell cycle regulation

Milton H Werner1, Chaowei Wu, Craig M Walsh

  • 1Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA. mwerner@portugal.rockefeller.edu

Cell Cycle (Georgetown, Tex.)
|November 15, 2006
PubMed

Insights

The Fas-associated death domain protein (FADD) acts as a signaling adaptor. New research shows FADD

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • The Fas-associated death domain protein (FADD) is a key adaptor protein in death receptor-mediated signaling.
  • Traditionally recognized for its role in initiating the death-inducing signaling complex (DISC) during apoptosis.
  • Emerging evidence suggests FADD possesses functions beyond its canonical apoptotic role.

Purpose of the Study:

  • To explore novel functions of FADD in both apoptotic and non-apoptotic cellular processes.
  • To investigate the impact of FADD's C-terminal chemical modifications on its signaling capabilities.
  • To understand how FADD complex assembly influences diverse cellular outcomes.

Main Methods:

  • Analysis of FADD's role in death receptor avidity.
  • Examination of FADD phosphorylation and its correlation with subcellular localization.
  • Investigation of FADD's involvement in high-valency complex formation within the plasma membrane and nucleus.

Main Results:

  • FADD exhibits unexpected properties beyond DISC nucleation.
  • Chemical modifications, particularly phosphorylation, influence FADD's subcellular localization and biological functions.
  • Novel high-valency FADD complexes may form in different cellular compartments, impacting signaling.

Conclusions:

  • FADD's function is dictated by differential complex assembly, not solely by its adaptor role.
  • FADD modulates both apoptosis and cell cycle progression through context-dependent complex formation.
  • Understanding FADD's dynamic interactions opens new avenues for targeting cellular processes.

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