Pharmacologic Inhibition of the Anaphase-Promoting Complex Induces A Spindle Checkpoint-Dependent Mitotic Arrest in the Absence of Spindle Damage
| dc.contributor.author | Zeng, Xing | |
| dc.contributor.author | Sigoillot, Frederic | |
| dc.contributor.author | Gaur, Shantanu | |
| dc.contributor.author | Choi, Sungwoon | |
| dc.contributor.author | Pfaff, Kathleen L. | |
| dc.contributor.author | Oh, Dong-Chan | |
| dc.contributor.author | Hathaway, Nathaniel | |
| dc.contributor.author | Dimova, Nevena | |
| dc.contributor.author | Cuny, Gregory D. | |
| dc.contributor.author | King, Randall W. | |
| dc.date.accessioned | 2020-03-10T17:31:41Z | |
| dc.date.available | 2020-03-10T17:31:41Z | |
| dc.date.issued | 10/19/2011 | |
| dc.description.abstract | Microtubule inhibitors are important cancer drugs that induce mitotic arrest by activating the spindleassembly checkpoint (SAC), which, in turn, inhibits the ubiquitin ligase activity of the anaphase-promotingcomplex (APC). Here, we report a small molecule, tosyl-L-arginine methyl ester (TAME), which binds to theAPC and prevents its activation by Cdc20 and Cdh1. A prodrug of TAME arrests cells in metaphase withoutperturbing the spindle, but nonetheless the arrest is dependent on the SAC. Metaphase arrest inducedby a proteasome inhibitor is also SAC dependent, suggesting that APC-dependent proteolysis is requiredto inactivate the SAC. We propose that mutual antagonism between the APC and the SAC yields a positivefeedback loop that amplifies the ability of TAME to induce mitotic arrest. | |
| dc.identifier.citation | Copyright 2010 Cancer Cell. This is a post-print version of a published paper that is available at: https://www.sciencedirect.com/science/article/pii/S1535610810003077. Recommended citation: Zeng, Xing, Frederic Sigoillot, Shantanu Gaur, Sungwoon Choi, Kathleen L. Pfaff, Dong-Chan Oh, Nathaniel Hathaway, Nevena Dimova, Gregory D. Cuny, and Randall W. King. "Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage." Cancer cell 18, no. 4 (2010): 382-395. doi: 10.1016/j.ccr.2010.08.010. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission. | |
| dc.identifier.uri | https://hdl.handle.net/10657/5961 | |
| dc.language.iso | en_US | |
| dc.publisher | Cancer Cell | |
| dc.title | Pharmacologic Inhibition of the Anaphase-Promoting Complex Induces A Spindle Checkpoint-Dependent Mitotic Arrest in the Absence of Spindle Damage | |
| dc.type | Article |