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The Apc5 Subunit of the Anaphase-Promoting Complex/Cyclosome Interacts with Poly(A) Binding Protein and Represses Internal Ribosome Entry Site-Mediated Translation

Nadejda Koloteva-Levine,^1, Dalia Pinchasi,¹ Idan Pereman,¹ Amit Zur,² Michael Brandeis,² and Orna Elroy-Stein^1*

Department of Cell Research & Immunology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv,¹ Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel²

Received 7 October 2003/ Returned for modification 20 November 2003/ Accepted 9 February 2004

The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G₁. We used a yeast three-hybrid screen to identify proteins that interact with the internal ribosome entry site (IRES) of platelet-derived growth factor 2 mRNA. Surprisingly, this screen identified Apc5, although it does not harbor a classical RNA binding domain. We found that Apc5 binds the poly(A) binding protein (PABP), which directly binds the IRES element. PABP was found to enhance IRES-mediated translation, whereas Apc5 overexpression counteracted this effect. In addition to its association with the APC/C complex, Apc5 binds much heavier complexes and cosediments with the ribosomal fraction. In contrast to Apc3, which is associated only with the APC/C and remains intact during differentiation, Apc5 is degraded upon megakaryocytic differentiation in correlation with IRES activation. Expression of Apc5 in differentiated cells abolished IRES activation. This is the first report implying an additional role for an APC/C subunit, apart from its being part of the APC/C complex.

Present address: Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom.

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