The Role of GADD34 (Growth Arrest and DNA Damage-Inducible Protein) in Regulating Apoptosis, Proliferation, and Protein Synthesis in Human Breast Cancer Cells
Abstract
GADD34 is a stress-induced proteins implicated in the control of protein synthesis and apoptosis. It is a major target of the oncogene c-myc. Myc is widely implicated in breast cancer and potently inhibits GADD34 expression. The goal of this proposal is to better understand the mechanism of GADD34 induced apoptosis and the implications of this to human breast cancer. Toward this goal we have analyzed the regulation of eIF2 alpha dephosphorylation by GADD34 and by its binding partner Inhibitor-i. We have demonstrated that proper subcellular localization of GADD34 is necessary for function. We have identified a novel domain that targets GADD34 to the endoplasmic reticulum, and a domain involved in PPl binding. Finally, we also examined the role of I-, 1 a CADD34 interacting protein that inhibits PPl, in inhibiting eIF2 alpha dephosphorylation and identified a novel domain necessary for in vivo function of 1-1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418759
Entities
People
- Douglas C. Weiser
Organizations
- Duke University Hospital