scholarly journals A Cul3-Based E3 Ligase Regulates Mitosis and is Required to Maintain the Spindle Assembly Checkpoint in Human Cells

Cell Cycle ◽  
2007 ◽  
Vol 6 (24) ◽  
pp. 3004-3010 ◽  
Author(s):  
Izabela Sumara ◽  
Matthias Peter
Cell Reports ◽  
2018 ◽  
Vol 22 (6) ◽  
pp. 1424-1438 ◽  
Author(s):  
Jonne A. Raaijmakers ◽  
Roy G.H.P. van Heesbeen ◽  
Vincent A. Blomen ◽  
Louise M.E. Janssen ◽  
Ferdy van Diemen ◽  
...  

2008 ◽  
Vol 183 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Evan C. Osmundson ◽  
Dipankar Ray ◽  
Finola E. Moore ◽  
Qingshen Gao ◽  
Gerald H. Thomsen ◽  
...  

Activation of the anaphase-promoting complex/cyclosome (APC/C) by Cdc20 is critical for the metaphase–anaphase transition. APC/C-Cdc20 is required for polyubiquitination and degradation of securin and cyclin B at anaphase onset. The spindle assembly checkpoint delays APC/C-Cdc20 activation until all kinetochores attach to mitotic spindles. In this study, we demonstrate that a HECT (homologous to the E6-AP carboxyl terminus) ubiquitin ligase, Smurf2, is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion or the expression of a catalytically inactive Smurf2 results in misaligned and lagging chromosomes, premature anaphase onset, and defective cytokinesis. Smurf2 inactivation prevents nocodazole-treated cells from accumulating cyclin B and securin and prometaphase arrest. The silencing of Cdc20 in Smurf2-depleted cells restores mitotic accumulation of cyclin B and securin. Smurf2 depletion results in enhanced polyubiquitination and degradation of Mad2, a critical checkpoint effector. Mad2 is mislocalized in Smurf2-depleted cells, suggesting that Smurf2 regulates the localization and stability of Mad2. These data indicate that Smurf2 is a novel mitotic regulator.


2016 ◽  
Vol 215 (2) ◽  
pp. 143-145 ◽  
Author(s):  
Michael Brandeis

The spindle assembly checkpoint arrests mitotic cells by preventing degradation of cyclin B1 by the anaphase-promoting complex/cyclosome, but some cells evade this checkpoint and slip out of mitosis. Balachandran et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601083) show that the E3 ligase CRL2ZYG11 degrades cyclin B1, allowing mitotic slippage.


Cell Reports ◽  
2016 ◽  
Vol 14 (8) ◽  
pp. 1829-1840 ◽  
Author(s):  
Thomas Wild ◽  
Marie Sofie Yoo Larsen ◽  
Takeo Narita ◽  
Julie Schou ◽  
Jakob Nilsson ◽  
...  

Cell Reports ◽  
2015 ◽  
Vol 12 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Conrad von Schubert ◽  
Fabien Cubizolles ◽  
Jasmine M. Bracher ◽  
Tale Sliedrecht ◽  
Geert J.P.L. Kops ◽  
...  

2016 ◽  
Vol 291 (21) ◽  
pp. 11252-11267 ◽  
Author(s):  
Florian Prinz ◽  
Vera Puetter ◽  
Simon J. Holton ◽  
Dorothee Andres ◽  
Christian M. Stegmann ◽  
...  

2008 ◽  
Vol 183 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Christopher B. O'Connell ◽  
Jadranka Lončarek ◽  
Polla Hergert ◽  
Antonis Kourtidis ◽  
Douglas S. Conklin ◽  
...  

The accuracy of chromosome segregation is enhanced by the spindle assembly checkpoint (SAC). The SAC is thought to monitor two distinct events: attachment of kinetochores to microtubules and the stretch of the centromere between the sister kinetochores that arises only when the chromosome becomes properly bioriented. We examined human cells undergoing mitosis with unreplicated genomes (MUG). Kinetochores in these cells are not paired, which implies that the centromere cannot be stretched; however, cells progress through mitosis. A SAC is present during MUG as cells arrest in response to nocodazole, taxol, or monastrol treatments. Mad2 is recruited to unattached MUG kinetochores and released upon their attachment. In contrast, BubR1 remains on attached kinetochores and exhibits a level of phosphorylation consistent with the inability of MUG spindles to establish normal levels of centromere tension. Thus, kinetochore attachment to microtubules is sufficient to satisfy the SAC even in the absence of interkinetochore tension.


Cell Reports ◽  
2018 ◽  
Vol 25 (9) ◽  
pp. 2317-2328.e5 ◽  
Author(s):  
Thomas Wild ◽  
Magda Budzowska ◽  
Susanne Hellmuth ◽  
Susana Eibes ◽  
Gopal Karemore ◽  
...  

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Christine C Lee ◽  
Bing Li ◽  
Hongtao Yu ◽  
Michael J Matunis

The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core. Our findings provide evidence of an important regulatory role for SUMO modification and binding in affecting APC/C activation and mitotic exit.


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