Mutation of <b> <i>hCDC4</i> </b> Leads to Cell Cycle Deregulation of Cyclin E in Cancer

• Susanna Ekholm Reed

  1Department of Molecular Biology, The Scripps Research Institute, La Jolla California;

• Charles H. Spruck

  1Department of Molecular Biology, The Scripps Research Institute, La Jolla California;

• Olle Sangfelt

  1Department of Molecular Biology, The Scripps Research Institute, La Jolla California;

• Frank van Drogen

  1Department of Molecular Biology, The Scripps Research Institute, La Jolla California;

• Elisabeth Mueller-Holzner

  3Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California

• Martin Widschwendter

  3Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California

• Anders Zetterberg

  2Cancer Center Karolinska, Karolinska Sjukhuset, Department of Oncology/Pathology, Stockholm, Sweden; and

• Steven I. Reed

  1Department of Molecular Biology, The Scripps Research Institute, La Jolla California;

抄録

hCDC4, the gene that encodes the F-box protein responsible for targeting cyclin E for ubiquitin-mediated proteolysis, has been found to be mutated in a number of primary cancers and cancer-derived cell lines. We have observed that functional inactivation of hCDC4 does not necessarily correlate with elevated levels of cyclin E in tumors. Here we show, however, that hCDC4 mutation in primary tumors correlates strongly with loss of cell cycle regulation of cyclin E. Similarly, a breast carcinoma-derived cell line mutated for hCDC4 exhibits cell cycle deregulation of cyclin E, but periodic expression is restored by reintroducing hCDC4 via retroviral transduction. Conversely, small interfering RNA-mediated silencing of hCdc4 deregulates cyclin E with respect to the cell cycle. These results indicate that hCdc4 function is an absolute prerequisite for cell cycle regulation of cyclin E levels, and loss of hCdc4 function is sufficient to deregulate cyclin E.

収録刊行物

• Cancer Research

  Cancer Research 64 (3), 795-800, 2004-02-01

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1361699994367268992
• NII論文ID: 30018589685
• DOI: 10.1158/0008-5472.can-03-3417
• ISSN: 15387445
• ISSN: 00085472
• Web Site: https://aacrjournals.org/cancerres/article-pdf/64/3/795/2522941/zch00304000795.pdf
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