Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates
Ordered progression of mitosis requires precise control in abundance of mitotic regulators. The anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays a key role by directing ubiquitin-mediated destruction of targets in a temporally and spatially defined manner. Specificity in APC/C tar...
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Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130097 |
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doaj-40b1e0e166304fcf848e8b67db416b0c2020-11-25T02:06:36ZengThe Royal SocietyOpen Biology2046-24412013-01-013910.1098/rsob.130097130097Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substratesMingwei MinUgo MayorCatherine LindonOrdered progression of mitosis requires precise control in abundance of mitotic regulators. The anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays a key role by directing ubiquitin-mediated destruction of targets in a temporally and spatially defined manner. Specificity in APC/C targeting is conferred through recognition of substrate D-box and KEN degrons, while the specificity of ubiquitination sites, as another possible regulated dimension, has not yet been explored. Here, we present the first analysis of ubiquitination sites in the APC/C substrate ubiquitome. We show that KEN is a preferred ubiquitin acceptor in APC/C substrates and that acceptor sites are enriched in predicted disordered regions and flanked by serine residues. Our experimental data confirm a role for the KEN lysine as an ubiquitin acceptor contributing to substrate destruction during mitotic progression. Using Aurora A and Nek2 kinases as examples, we show that phosphorylation on the flanking serine residue could directly regulate ubiquitination and subsequent degradation of substrates. We propose a novel layer of regulation in substrate ubiquitination, via phosphorylation adjacent to the KEN motif, in APC/C-mediated targeting.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130097ubiquitinationubiquitin acceptor(apc/c)kendegronaurora a |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mingwei Min Ugo Mayor Catherine Lindon |
spellingShingle |
Mingwei Min Ugo Mayor Catherine Lindon Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates Open Biology ubiquitination ubiquitin acceptor (apc/c) ken degron aurora a |
author_facet |
Mingwei Min Ugo Mayor Catherine Lindon |
author_sort |
Mingwei Min |
title |
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates |
title_short |
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates |
title_full |
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates |
title_fullStr |
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates |
title_full_unstemmed |
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates |
title_sort |
ubiquitination site preferences in anaphase promoting complex/cyclosome (apc/c) substrates |
publisher |
The Royal Society |
series |
Open Biology |
issn |
2046-2441 |
publishDate |
2013-01-01 |
description |
Ordered progression of mitosis requires precise control in abundance of mitotic regulators. The anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays a key role by directing ubiquitin-mediated destruction of targets in a temporally and spatially defined manner. Specificity in APC/C targeting is conferred through recognition of substrate D-box and KEN degrons, while the specificity of ubiquitination sites, as another possible regulated dimension, has not yet been explored. Here, we present the first analysis of ubiquitination sites in the APC/C substrate ubiquitome. We show that KEN is a preferred ubiquitin acceptor in APC/C substrates and that acceptor sites are enriched in predicted disordered regions and flanked by serine residues. Our experimental data confirm a role for the KEN lysine as an ubiquitin acceptor contributing to substrate destruction during mitotic progression. Using Aurora A and Nek2 kinases as examples, we show that phosphorylation on the flanking serine residue could directly regulate ubiquitination and subsequent degradation of substrates. We propose a novel layer of regulation in substrate ubiquitination, via phosphorylation adjacent to the KEN motif, in APC/C-mediated targeting. |
topic |
ubiquitination ubiquitin acceptor (apc/c) ken degron aurora a |
url |
https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130097 |
work_keys_str_mv |
AT mingweimin ubiquitinationsitepreferencesinanaphasepromotingcomplexcyclosomeapccsubstrates AT ugomayor ubiquitinationsitepreferencesinanaphasepromotingcomplexcyclosomeapccsubstrates AT catherinelindon ubiquitinationsitepreferencesinanaphasepromotingcomplexcyclosomeapccsubstrates |
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