Unknown

Dataset Information

0

Role of ubiquitylation of components of mitotic checkpoint complex in their dissociation from anaphase-promoting complex/cyclosome.


ABSTRACT: The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of MCC. Previous studies indicated that the dissociation of APC/C-bound MCC requires ubiquitylation and suggested that the target of ubiquitylation is the Cdc20 component of MCC. However, it remained unknown how ubiquitylation causes the release of MCC from APC/C and its disassembly and whether ubiquitylation of additional proteins is involved in this process. We find that ubiquitylation causes the dissociation of BubR1 from Cdc20 in MCC and suggest that this may lead to the release of MCC components from APC/C. BubR1 in MCC is ubiquitylated by APC/C, although to a lesser degree than Cdc20. The extent of BubR1 ubiquitylation was markedly increased in recombinant MCC that contained a lysine-less mutant of Cdc20. Mutation of lysine residues to arginines in the N-terminal region of BubR1 partially inhibited its ubiquitylation and slowed down the release of MCC from APC/C, provided that Cdc20 ubiquitylation was also blocked. It is suggested that ubiquitylation of both Cdc20 and BubR1 may be involved in their dissociation from each other and in the release of MCC components from APC/C.

SUBMITTER: Sitry-Shevah D 

PROVIDER: S-EPMC5828624 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Role of ubiquitylation of components of mitotic checkpoint complex in their dissociation from anaphase-promoting complex/cyclosome.

Sitry-Shevah Danielle D   Kaisari Sharon S   Teichner Adar A   Miniowitz-Shemtov Shirly S   Hershko Avram A  

Proceedings of the National Academy of Sciences of the United States of America 20180205 8


The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of  ...[more]

Similar Datasets

| S-EPMC2989460 | biostudies-literature
| S-EPMC6496518 | biostudies-literature
| S-EPMC2077894 | biostudies-literature
| S-EPMC549351 | biostudies-literature
| S-EPMC8182066 | biostudies-literature
| S-EPMC2864710 | biostudies-literature
| S-EPMC3606461 | biostudies-literature
| S-EPMC3787748 | biostudies-literature
| S-EPMC1797942 | biostudies-literature
| S-EPMC8650582 | biostudies-literature