Interaction of p53 with 14-3-3
Abstract
The p53 tumor suppressor protein is a sequence-specific DNA binding transcription factor that induces cell cycle arrest or apoptosis in response to DNA damage. We had previously demonstrated that ionizing radiation (IR) leads to association of p53 with 14-3-3 in breast cancer cells and hypothesized that this association activates the tumor suppressor function of p53. To test this hypothesis, we had proposed to determine whether the interaction of p53 with 14-3-3 affects: (1) the sequence-specific DNA binding activity of p53 (months 1-12); (2) the cell cycle arrest and/or apoptotic functions of p53 (months 13-24); and (3) p53 intracellular localization and half-life (months 25-36). During the first year of funding we have began to address Tasks 1 and 2. We have established that the interaction of p53 with 14-3-3 is critical for the ability of p53 to induce cell cycle arrest (Task 2), but appears to not affect the DNA binding activity of p53 (Task 1). Overall, the results support the initial hypothesis that the interaction of p53 with 14-3-3 activates the tumor suppressor function of p53, but also indicate that the mechanism might not be through activation of the sequence-specific DNA binding activity of p53, as originally thought.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA385429
Entities
People
- Thanos Halazonetis
Organizations
- Wistar Institute