Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome

Authors:

R. Roshini Beenukumar1,#, Daniela Gödderz1,2,#, R. Palanimurugan1,3, and R. Jürgen Dohmen1

doi: 10.15698/mic2015.06.206
Volume 2, pp. 197 to 205, published 20/05/2015.

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Affiliations:

1 Institute for Genetics, University of Cologne, Biocenter, Zülpicher Str. 47a, D-50674 Cologne, Germany.

2 Present address: Karolinska Institute, Department for Cell- and Molecular Biology, Von Eulers väg 3, 171 77 Stockholm. E-mail: daniela.godderz@ki.se

3 Present address: Center for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad 500007, India. E-mail: murugan@ccmb.res.in

# These authors contributed equally to this study.

Keywords: 

antizyme, ODC, polyamines, proteasome, ubiquitin

Corresponding Author(s):

R. Jürgen Dohmen, University of Cologne, Biocenter, Institute for Genetics; Zülpicher Str. 47a, D-50674 Cologne j.dohmen@uni-koeln.de

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

R. Roshini Beenukumar, Daniela Gödderz, R. Palanimurugan, and R. Jürgen Dohmen (2015). Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome. Microbial Cell 2(6): 197-207.

© 2015 Beenukumar et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the proteasome in a reconstituted system using purified components. In these assays, spermine shows a greater effect than spermidine. By contrast, polyamines do not have any stimulatory effect on the degradation of ubiquitin-dependent substrates.