Accession Number:

ADA443994

Title:

The Role of GADD34 (Growth Arrest and DNA Damage-Inducible Protein) in Regulating Apoptosis, Proliferation, and Protein Synthesis in Human Breast Cancer Cells

Descriptive Note:

Annual summary 1 Jul 2002-30 Jun 2005

Corporate Author:

DUKE UNIV MEDICAL CENTER DURHAM NC

Personal Author(s):

Report Date:

2005-07-01

Pagination or Media Count:

29.0

Abstract:

The proto-oncogene c-myc has been widely implicated in human cancer. One of the major cellular targets of c-myc is the stress-induced gene GADD34. GADD34 is a potent apoptotic-inducer, but c-myc expression potently inhibits GADD34 expression, indicating that GADD34 may be an important target of c-myc-mediated oncogenesis2. 3ADD34 is a scaffolding protein that interacts with several proteins including Protein Phosphatase 1 PP1 and a PP1 inhibitor, Inhibitor-1 I-1 sub 3. GADD34 binds and targets PP1 to the eukaryotic inhibitor factor 2 alpha eIF2 alpha and promotes its dephosphorylation. The reversible phosphorylation of eIF2 alpha is a critical step in the control of translation by stress signaling and is the target of several kinases. Interestingly, the anti-cancer drug methylselenocysteine MSC or Avemar both promotes apoptosis and GADD34 expression in human cancer cells sub 4. Another drug, salubrinal, inhibits the GADD34-PP1 complex, and inhibits apoptosis in mammalian cells sub 5. This indicates that GADD34 could prove to be an important target for anticancer therapies.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE