Mechanism of p53 Dependent Apoptosis and its Role in Breast Cancer Therapy
Abstract
The p53 protein contains several functional domains necessary for inducing cell cycle arrest and apoptosis, that is, activation domain 1 and 2, the proline-rich domain, and the C-terminal basic domain. To further determine the role of each p53 functional domain, we found that deletion of; or mutation at, activation domain 2 abrogates the apoptotic activity but not cell cycle arrest. We also found that at least two of the three domains, that is, activation domain 1 and 2 and the proline-rich domain, are necessary for cell cycle arrest. Interestingly, we found that deletion of activation domain 1 alleviates the requirement of the C-terminal basic domain for apoptotic activity. Furthermore, we found that activation domain 2 and the proline-rich domain form an activation domain for inducing pro-apoptotic genes and the C-terminal basic domain is required for maintaining this activation domain competent for transactivation. As an extension of our studies to determine how p53 functions as a tumor suppressor, we identified two novel p53 target genes, Dickkopf-1 (Dkk-l), an antagonist of the Wnt oncogenic pathway, and TAP1, a transporter of major histocompatibility class I antigens. This suggests that p53 may suppress transformation by Wnt and play a role in immunosurveillance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA387993
Entities
People
- Xinbin Chen
Organizations
- Medical College of Georgia