Identification of Novel Targets of the Human Cell Cycle Regulatory Protein Cdc34
Abstract
A characteristic feature of human malignancy is the loss of normal cell cycle control. One mechanism by which proteins control the cell cycle is by ubiquitin-mediated destruction of cell cycle regulators. CDC34, a gene essential for mitotic cell division in yeast encodes an enzyme required for degradation of yeast cell cycle regulators. The goal of this project is to understand the role of human Cdc34 in cell cycle transition in normal and malignant mammary cells. We hypothesize that human Cdc34 is a cell cycle regulatory protein which modulates the stability of specific cellular proteins by targeting them for degradation. The targets of mammalian Cdc34 are not presently known. We have used a genetic assay called two-hybrid cloning to identify proteins that interact with mammalian Cdc34, screening 1.5 million human cDNAs. 30 cDNA clones found to be active in this assay have been isolated and are currently being analyzed. Surprisingly, four of these clones are known to be involved in the control of meiosis and spermatogenesis, one also has a distinct role in DNA double strand break repair. Thus, it appears from our studies that human Cdc34 may have a novel role in meiosis, recombination, and response to DNA damage in higher organisms by specifically targeting these regulators for ubiquitination. Further studies are currently in progress to characterize the Cdc34-mediated regulation of these interactors and their physiological role in the cell cycle progression and development of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADB232086
Entities
People
- Debananda Pati
Organizations
- Baylor College of Medicine