Controlling Cell Death through Post-translational Modifications of DED Proteins

Trends Cell Biol. 2020 May;30(5):354-369. doi: 10.1016/j.tcb.2020.02.006. Epub 2020 Mar 29.

Abstract

Apoptosis is a form of programmed cell death, deregulation of which occurs in multiple disorders, including neurodegenerative and autoimmune diseases as well as cancer. The formation of a death-inducing signaling complex (DISC) and death effector domain (DED) filaments are critical for initiation of the extrinsic apoptotic pathway. Post-translational modifications (PTMs) of DED-containing DISC components such as FADD, procaspase-8, and c-FLIP comprise an additional level of apoptosis regulation, which is necessary to overcome the threshold for apoptosis induction. In this review we discuss the influence of PTMs of FADD, procaspase-8, and c-FLIP on DED filament assembly and cell death induction, with a focus on the 3D organization of the DED filament.

Keywords: DED proteins; SUMOylation; apoptosis; nitrosylation; phosphorylation; ubiquitylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Caspase 8 / metabolism
  • Cell Death
  • Death Domain Receptor Signaling Adaptor Proteins / metabolism*
  • Humans
  • Models, Biological
  • Protein Processing, Post-Translational*
  • Signal Transduction

Substances

  • Death Domain Receptor Signaling Adaptor Proteins
  • Caspase 8