Antizyme Activation in Chemotherapy and Chemoprevention
Abstract
Antizyme is a small, labile protein central to the regulation of polyamines and a likely candidate to mediate polyamine depletion as cancer therapy. Antizyme exists in several different forms in cells that may reflect variable function or cellular localization. To sort out the origin, modification, function and localization of the various forms of antizyme, a cell line with an inducible Az-I construct that can only result in protein synthesized from the first start site was produced. Western blot analysis showed that the mutated antizyme gene, when expressed in cells, produces two proteins distinct in molecular weight. One of the forms appears to be derived by proteolytic truncation of the N- terminus. These forms of antizyme behave as native antizyme with respect to activity in binding and inhibiting ODC, as well as down-regulating the polyamine transport system. Characterization of the N-terminal truncation of antizyme was attempted by various means. Unfortunately, a specific cleavage site could not be determined. These results suggest that native antizyme is post-translationally modified and this modification may play a role in the regulation of antizyme.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2003
- Accession Number
- ADA420170
Entities
People
- John L. Mitchell
- Sandra L. Moore
Organizations
- Northern Illinois University