The Regulator Interactions of p21 and PCNA in Human Breast Cancer
Abstract
Proliferating cell nuclear antigen (PCNA) is a multifunctional protein essential for DNA replication and DNA repair. Recently, our laboratory has shown that when resolved using two-dimensional polyacrylamide gel electrophoresis (2D PAGE) PCNA focuses at distinct isoelectric point(s) (pI). It was subsequently noted that this focusing pattern was different when non-malignant and malignant breast cells were compared. The PCNA present in non-malignant breast cells focuses at one pI on 2D PAGE while the PCNA present in malignant breast cells consistently focuses at two distinct pIs. In order to explore the functional consequences of the alteration of PCNA in malignant breast cells, we have begun to examine its interaction with cell cycle inhibitor p21(sup WAF1/CIP1/SDI1). Through its interaction with PCNA, p21 inhibits DNA replication in response to DNA damage. Theoretically, p21 stops the cell from replicating damaged DNA and allocates time needed for DNA repair. Paradoxically, PCNA also functions in repair, and there is a multitude of conflicting data on the inhibitory role of p21 in DNA repair. Therefore, we have begun to elucidate the structure and location of the post-translational modification on PCNA and have shown that p21 differentially interacts with PCNA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA400020
Entities
People
- Derek J. Hoelz
- Linda H. Malkas
Organizations
- University of Maryland, Baltimore