G1 Cell Cycle Control by Regulated Proteolysis in Normal and Tumorigenic Breast Cells
Abstract
The p53 tumor suppressor gene mediates a pathway leading to GI cell cycle arrest and/or apoptosis. p53 function is frequently altered in breast cancer and other human cancers. p53 protein is kept at a low level during normal cell growth by its short half-life and is stabilized following oncogenic stimulation and DNA damage. This research is exploring factors that contribute to the stabilization of p53 after oncogenic stimulation. MDM2 oncoprotein binds to and targets p53 for degradation in the cytoplasm. The tumor suppressor ARF stabilizes p53 by blocking the nuclear export of both p53 and MDM2. In work under this award, it was shown that ARF has biological activity independent of p53. Overexpression of ARF impedes DNA synthesis, resulting in accumulation of cells in S phase. Hence, ARF induction induces predominantly Gl arrest if p53 is present or S-phase retardation in the absence of p53. The Principal Investigator (PI) also obtained evidence that p53 protein contains two nuclear exporting signal sequences, one specific for MDM2 and one whose activity is independent of MDM2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA404571
Entities
People
- Yue Xiong
Organizations
- University of North Carolina at Chapel Hill