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Targeting the p27 E3 ligase SCF Skp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy by Qing Chen, Weilin Xie, Deborah.

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Presentation on theme: "Targeting the p27 E3 ligase SCF Skp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy by Qing Chen, Weilin Xie, Deborah."— Presentation transcript:

1 Targeting the p27 E3 ligase SCF Skp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy by Qing Chen, Weilin Xie, Deborah J. Kuhn, Peter M. Voorhees, Antonia Lopez- Girona, Derek Mendy, Laura G. Corral, Veronique Plantevin Krenitsky, Weiming Xu, Laure Moutouh-de Parseval, David R. Webb, Frank Mercurio, Keiichi I. Nakayama, Keiko Nakayama, and Robert Z. Orlowski Blood Volume 111(9):4690-4699 May 1, 2008 ©2008 by American Society of Hematology

2 CpdA inhibits p27Kip1 ubiquitination and turnover. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology

3 Stabilization of SCFSkp2 substrates by CpdA in multiple myeloma cells. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology

4 SCFSkp2 inhibition induces caspase-independent apoptosis and cell-cycle arrest. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology

5 Inhibition of SCFSkp2 induces autophagic cell death. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology

6 CpdA overcomes drug resistance and induces chemosensitization. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology

7 CpdA is active in patient-derived neoplastic cells. Qing Chen et al. Blood 2008;111:4690-4699 ©2008 by American Society of Hematology


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