The Role of Ubiquitin-Mediated Proteolysis of Cyclin D in Breast Cancer
Abstract
Studies have indicated that cyclin D protein levels are modulated post-transcriptionally by the ubiquitin-mediated protein degradation pathway. The specific E2 and E3 enzymes postulated to target cyclin D for ubiquitination are the ubiquitin conjugating enzyme, CDC34, and the ubiquitin protein ligase called SCF/ring (Skp1, Cullin F-box, ring protein). Our findings indicate that CDC34 is phosphorylated by Casein Kinase 2 (CK2) on five carboxyl-terminal residues. Mutation of these residues of CDC34 significantly alter the cell localization of CDC34 and potentially its function with the SCF complex. A recent study has shown that the breast cancer cell line, MCF-7, highly over-expresses cyclin D and is significantly reduced for SCF-mediated ubiquitination activity specific for cyclin D. Therefore, we propose CDC34-SCF activity specific for cyclin D is regulated by CDC34 phosphorylation, compartmentalization, and protein-protein interactions. The goal of our studies is to understand the biological significance of CDC34 phosphorylation and its impact in cyclin D protein regulation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA416662
Entities
People
- Karen L. Block
Organizations
- University of Texas Health Science Center at San Antonio