Zeng, XingSigoillot, FredericGaur, ShantanuChoi, SungwoonPfaff, Kathleen L.Oh, Dong-ChanHathaway, NathanielDimova, NevenaCuny, Gregory D.King, Randall W.2020-03-102020-03-1010/19/2011Copyright 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.https://hdl.handle.net/10657/5961Microtubule 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.en-USArticle