PMID- 20951947
OWN - NLM
STAT- MEDLINE
DCOM- 20101103
LR  - 20211020
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 18
IP  - 4
DP  - 2010 Oct 19
TI  - Pharmacologic inhibition of the anaphase-promoting complex induces a spindle 
      checkpoint-dependent mitotic arrest in the absence of spindle damage.
PG  - 382-95
LID - 10.1016/j.ccr.2010.08.010 [doi]
AB  - Microtubule inhibitors are important cancer drugs that induce mitotic arrest by 
      activating the spindle assembly checkpoint (SAC), which, in turn, inhibits the 
      ubiquitin ligase activity of the anaphase-promoting complex (APC). Here, we 
      report a small molecule, tosyl-L-arginine methyl ester (TAME), which binds to the 
      APC and prevents its activation by Cdc20 and Cdh1. A prodrug of TAME arrests 
      cells in metaphase without perturbing the spindle, but nonetheless the arrest is 
      dependent on the SAC. Metaphase arrest induced by a proteasome inhibitor is also 
      SAC dependent, suggesting that APC-dependent proteolysis is required to 
      inactivate the SAC. We propose that mutual antagonism between the APC and the SAC 
      yields a positive feedback loop that amplifies the ability of TAME to induce 
      mitotic arrest.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Zeng, Xing
AU  - Zeng X
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Sigoillot, Frederic
AU  - Sigoillot F
FAU - Gaur, Shantanu
AU  - Gaur S
FAU - Choi, Sungwoon
AU  - Choi S
FAU - Pfaff, Kathleen L
AU  - Pfaff KL
FAU - Oh, Dong-Chan
AU  - Oh DC
FAU - Hathaway, Nathaniel
AU  - Hathaway N
FAU - Dimova, Nevena
AU  - Dimova N
FAU - Cuny, Gregory D
AU  - Cuny GD
FAU - King, Randall W
AU  - King RW
LA  - eng
GR  - R56 GM066492/GM/NIGMS NIH HHS/United States
GR  - P50 CA089393/CA/NCI NIH HHS/United States
GR  - GM66492/GM/NIGMS NIH HHS/United States
GR  - GM085923/GM/NIGMS NIH HHS/United States
GR  - F32 GM085923/GM/NIGMS NIH HHS/United States
GR  - R01 GM066492/GM/NIGMS NIH HHS/United States
GR  - CA089393/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Mutant Proteins)
RN  - 0 (Prodrugs)
RN  - 0 (Proteasome Inhibitors)
RN  - 901-47-3 (Tosylarginine Methyl Ester)
RN  - EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes)
RN  - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Anaphase-Promoting Complex-Cyclosome
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Metaphase/drug effects
MH  - Microtubules/drug effects/metabolism
MH  - Mitosis/*drug effects
MH  - Mutant Proteins/metabolism
MH  - Prodrugs/pharmacology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Proteasome Inhibitors
MH  - Protein Binding/drug effects
MH  - Protein Biosynthesis/drug effects
MH  - Spindle Apparatus/*drug effects/*pathology
MH  - Tosylarginine Methyl Ester/*pharmacology
MH  - Ubiquitin-Protein Ligase Complexes/*antagonists & inhibitors/metabolism
MH  - Xenopus
PMC - PMC2957475
MID - NIHMS237726
COIS- The authors declare no financial conflict of interest.
EDAT- 2010/10/19 06:00
MHDA- 2010/11/04 06:00
PMCR- 2011/10/19
CRDT- 2010/10/19 06:00
PHST- 2010/04/09 00:00 [received]
PHST- 2010/07/01 00:00 [revised]
PHST- 2010/08/10 00:00 [accepted]
PHST- 2010/10/19 06:00 [entrez]
PHST- 2010/10/19 06:00 [pubmed]
PHST- 2010/11/04 06:00 [medline]
PHST- 2011/10/19 00:00 [pmc-release]
AID - S1535-6108(10)00307-7 [pii]
AID - 10.1016/j.ccr.2010.08.010 [doi]
PST - ppublish
SO  - Cancer Cell. 2010 Oct 19;18(4):382-95. doi: 10.1016/j.ccr.2010.08.010.