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Overexpression of the Anaphase Promoting Complex/Cyclosome Inhibitor Emi1 Leads to Tetraploidy and Genomic Instability of p53-Deficient Cells
Norman L. Lehman, Emmy W. Verschuren, Jerry Y. Hsu, Athena M. Cherry and Peter K. Jackson
volume 5 | issue 14
15 july 2006Pages: 1569 - 1573
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The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls the cell cycle by directing the ubiquitin-dependent proteolysis of Sphase and mitosis promoting factors. Emi1 is an E2F transcriptional target that drives cell cycle progression from G1/S through early mitosis by inhibiting the APC/C’s ubiquitin ligase activity, and thus facilitates accumulation of APC/C substrates. Using cell culture model systems, we found that Emi1 overexpression leads to proliferation, tetraploidy and genome instability of cells deficient for p53. We propose that loss of pRb repression of E2F-mediated transcription causing misregulation of Emi1 and APC/C substrates results in the generation of tetraploidy and proliferation of genomically unstable cells in the absence of normal p53 function. This represents a potentially important mechanism by which pRb and p53 dysfunction may contribute to tumorigenesis through the generation of genomic instability.
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.