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) : Welser, Douglas C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a443994.pdf


Report Date : Jul 2005


Pagination or Media Count : 29


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.


Descriptors :   *BREAST CANCER , STRESSES , DAMAGE , MAMMALS , HUMANS , PROTEINS , ARRESTING(PROCESS) , DEOXYRIBONUCLEIC ACIDS , SIGNALS , THERAPY , APOPTOSIS , DRUGS , CELLS(BIOLOGY) , ANTIGENS , BIOSYNTHESIS , GROWTH(PHYSIOLOGY) , PHOSPHORYLATION , PHOSPHORUS TRANSFERASES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE