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Vol. 16, Issue 5, 2181-2190, May 2005

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EAPP, a Novel E2F Binding Protein That Modulates E2F-dependent Transcription

Michael Novy ^*, Regina Pohn , Peter Andorfer ^*, Tina Novy-Weiland , Barbara Galos ^*, Ludwig Schwarzmayr ^*, and Hans Rotheneder ^*

^* Max F. Perutz Laboratories, Department of Medical Biochemistry, University Departments at the Vienna Biocenter, Medical University of Vienna, A-1030 Vienna, Austria; Department of Biochemistry, Institute of Biochemistry and Molecular Cell Biology, A-1030 Vienna, Austria; and Baxter Bioscience, A-1220 Vienna, Austria

Submitted November 8, 2004; Accepted February 8, 2005
Monitoring Editor: William Tansey

E2F transcription factors play an essential role in cell proliferation and apoptosis and their activity is frequently deregulated in human cancers. In a yeast two-hybrid screen we identified a novel E2F-binding protein. Due to its strong phosphorylation we named it EAPP (e2F-associated phosphoprotein). EAPP is localized in the nucleus and interacts with E2F-1, E2F-2, and E2F-3, but not with E2F-4. Examination of a number of human cell lines revealed that EAPP levels are elevated in most transformed cells. Moreover, EAPP mRNA was detected in all investigated human tissues in varying amounts. EAPP is present throughout the cell cycle but disappears during mitosis. In transfection assays with reporters controlled by either an artificial E2F-dependent promoter or the murine thymidine kinase promoter, EAPP increased the activation caused by E2F-1 but not by E2F-4. Surprisingly, the promoter of the p14^ARF gene, which was also activated by E2F-1, became repressed by EAPP. Overexpression of EAPP in U2OS cells resulted in a significant increase of cells in S-phase, whereas RNAi-mediated knock down of EAPP reduced the fraction of cells in S-phase. Taken together, these data suggest that EAPP modulates E2F-regulated transcription, stimulates proliferation, and may be involved in the malignant transformation of cells.

Abbreviations used: EAPP, E2F-associated phosphoprotein; GST, glutathione-S-transferase; GFP, green fluorescent protein; CIP, calf intestine ALP.

Address correspondence to: Hans Rotheneder (Johann.Rotheneder{at}univie.ac.at).

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