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Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells

M J Clemens1, M Bushell, I W Jeffrey

  • 1Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK. M.Clemens@sghms.ac.uk

Cell Death and Differentiation
|July 13, 2000
PubMed

Insights

During apoptosis, protein synthesis initiation is inhibited by modifications to key translation factors. Caspase activity and factor cleavage play crucial roles in regulating this process.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Protein synthesis is rapidly downregulated during apoptosis.
  • This inhibition occurs at the level of polypeptide chain initiation.

Purpose of the Study:

  • To review modifications of initiation factors during apoptosis.
  • To explore signaling pathways regulating translation during this process.
  • To discuss the implications of these changes for understanding apoptosis.

Main Methods:

  • Review of existing literature on apoptosis and protein synthesis.
  • Analysis of caspase-dependent cleavage of initiation factors (eIF4G, eIF4B, eIF2alpha, eIF3).
  • Examination of phosphorylation of the alpha subunit of initiation factor eIF2.

Main Results:

  • Apoptosis involves phosphorylation of eIF2 alpha subunit and caspase-dependent cleavage of eIF4G, eIF4B, eIF2alpha, and eIF3.
  • Cleavage products may regulate the translational machinery.
  • Caspase inhibition partially protects protein synthesis.

Conclusions:

  • Initiation factor modifications are central to translational control during apoptosis.
  • Understanding these events is key to comprehending cellular changes in apoptosis.
  • Further research into signaling pathways is warranted.

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