Antizyme Activation in Chemotherapy and Chemoprevention

Abstract

Antizyme is a small, labile protein important in the regulation of polyamines and a likely candidate to mediate polyamine depletion as cancer therapy. Once thought of as a single protein, antizyme has been found to actually consist of at least four different forms in cells. These forms are distinct in their molecular weight, stability and response to osmotic stress. To determine what forms originate from the first start site of AZ-1 and what post-translational modifications occur, Antizyme constructs with the second start site mutated were made and transfected into rat hepatoma (HTC) and Chinese hamster ovary (CHO) cells. Western blot analysis showed that the mutated antizyme gene, when expressed in cells, produces two proteins distinct in molecular weight. Only one band was expected, and when expressed in a cell-free system only one band was seen. The second, smaller band found in cells can only be explained by post-translational modification. These forms of antizyme behave as native antizyme with respect to activity in binding to and inhibiting ODC as well as cellular localization based on cellular fractionation experiments. These results suggests that native antizyme is post-translationally modified and this modification may play a role in the regulation of antizyme activity.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2002
Accession Number
ADA405302

Entities

People

  • Sandra L. Moore

Organizations

  • Northern Illinois University

Tags

DTIC Thesaurus Topics

  • Amines
  • Amino Acids
  • Anatomy
  • Antibodies
  • Biological Sciences
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chemotherapy
  • Confocal Microscopy
  • Drug Therapy
  • Fractionation
  • Molecular Weight
  • Neoplasms
  • Regulations
  • Therapy
  • Universities

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry
  • Solar Photovoltaics and Thermoelectric Devices.

Technology Areas

  • Biotechnology