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J. Biol. Chem., Vol. 283, Issue 8, 4528-4534, February 22, 2008

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Yeast Antizyme Mediates Degradation of Yeast Ornithine Decarboxylase by Yeast but Not by Mammalian Proteasome

NEW INSIGHTS ON YEAST ANTIZYME^*

Ziv Porat, Guy Landau, Zippi Bercovich, Dasha Krutauz, Michael Glickman, and Chaim Kahana¹

From the Department of Molecular Genetics, The Weizmann Institute of Science, 1 Hertzel St., Rehovot 76100 and the Department of Biology, Technion, Israel Institute of Technology, Haifa 32000, Israel

Mammalian antizyme (mAz) is a central element of a feedback circuit regulating cellular polyamines by accelerating ornithine decarboxylase (ODC) degradation and inhibiting polyamine uptake. Although yeast antizyme (yAz) stimulates the degradation of yeast ODC (yODC), we show here that it has only a minor effect on polyamine uptake by yeast cells. A segment of yODC that parallels the Az binding segment of mammalian ODC (mODC) is required for its binding to yAz. Although demonstrating minimal homology to mAz, our results suggest that yAz stimulates yODC degradation via a similar mechanism of action. We demonstrate that interaction with yAz provokes degradation of yODC by yeast but not by mammalian proteasomes. This differential recognition may serve as a tool for investigating proteasome functions.

Received for publication, September 27, 2007 , and in revised form, November 29, 2007.

^* This work was supported in part by the Israel Academy of Sciences and Humanities, the Y. Leon Benoziyo Institute for Molecular Medicine, the M. D. Moross Institute for Cancer Research, and the Leo and Julia Forchheimer center for Molecular Genetics at the Weizmann Institute of Science (to C. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The incumbent of the Jules J. Mallon Professorial chair in Biochemistry. To whom correspondence should be addressed: Tel.: 972-8-9344577; Fax: 972-8-934-4199; E-mail: chaim.kahana{at}weizmann.ac.il.

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