Regulated degradation of ornithine decarboxylase requires interaction with the polyamine-inducible protein antizyme.
Open Access
- 1 August 1992
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 12 (8) , 3556-3562
- https://doi.org/10.1128/mcb.12.8.3556
Abstract
Intracellular degradation of vertebrate ornithine decarboxylase (ODC) is accelerated by polyamines, the products of the pathway controlled by ODC. Antizyme, a reversible, tightly binding protein inhibitor of ODC activity, is believed to be involved in this process. Mouse and Trypanosoma brucei ODCs are structurally similar, but the trypanosome enzyme, unlike that of the mouse, is not regulated by intracellular polyamines when expressed in hamster cells (L. Ghoda, D. Sidney, M. Macrae, and P. Coffino, Mol. Cell. Biol. 12:2178-2185, 1992). We found that mouse ODC interacts with antizyme in vitro but trypanosome ODC does not. To localize the region necessary for binding, we made a series of enzymatically active chimeric mouse-trypanosome ODCs and tested them for antizyme interaction. Replacing residues 117 to 140 within the 461-amino-acid mouse ODC sequence with the equivalent region of trypanosome ODC disrupted both antizyme binding and in vivo regulation. Formation of an antizyme-ODC complex is therefore required for regulated degradation. ImagesKeywords
This publication has 27 references indexed in Scilit:
- Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition.Published by Elsevier ,2021
- Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extensionPublished by Elsevier ,2003
- Structural elements of ornithine decarboxylase required for intracellular degradation and polyamine-dependent regulation.Molecular and Cellular Biology, 1992
- Analyses of Ornithine Decarboxylase Antizyme mRNA with a cDNA Cloned from Rat Liver1The Journal of Biochemistry, 1990
- Regulation of ornithine decarboxylase mRNA translation by polyamines. Studies using a cell-free system and a cell line with an amplified ornithine decarboxylase gene.Journal of Biological Chemistry, 1988
- Spermidine mediates degradation of ornithine decarboxylase by a non‐lysosomal, ubiquitin‐independent mechanismJournal of Cellular Physiology, 1987
- Amino Acid Sequences Common to Rapidly Degraded Proteins: The PEST HypothesisScience, 1986
- Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells.Molecular and Cellular Biology, 1986
- Control of ornithine decarboxylase in Chinese hamster ovary cells by polyamines. Translational inhibition of synthesis and acceleration of degradation of the enzyme by putrescine, spermidine, and spermine.Journal of Biological Chemistry, 1986
- Induction of a protein inhibitor to ornithine decarboxylase by the end products of its reaction.Proceedings of the National Academy of Sciences, 1976