The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ribosome entry site-mediated translation.
The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G(1). 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.
Koloteva-Levine
Nadejda
N
Department of Cell Research & Immunology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel.
Pinchasi
Dalia
D
Pereman
Idan
I
Zur
Amit
A
Brandeis
Michael
M
Elroy-Stein
Orna
O
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064193:Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D006801:Humans; D046911:Macromolecular Substances; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
C577375:ANAPC5 protein, human; C577378:APC5 protein, S cerevisiae; D064193:Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D039102:Poly(A)-Binding Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C450100:pab1 protein, S cerevisiae; D012313:RNA; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome