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TitleMolecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation.
Journal, issue, pagesCell Rep, Vol. 34, Issue 13, Page 108929, Year 2021
Publish dateMar 30, 2021
AuthorsStanislau Yatskevich / Jessie S Kroonen / Claudio Alfieri / Thomas Tischer / Anna C Howes / Linda Clijsters / Jing Yang / Ziguo Zhang / Kaige Yan / Alfred C O Vertegaal / David Barford /
PubMed AbstractThe anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the ...The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand the structural and functional consequences of APC/C SUMOylation, we reconstituted SUMOylated APC/C for electron cryo-microscopy and biochemical analyses. SUMOylation of the APC/C causes a substantial rearrangement of the WHB domain of APC/C's cullin subunit (APC2). Although APC/C SUMOylation results in a modest impact on normal APC/C activity, repositioning APC2 reduces the affinity of APC/C for the mitotic checkpoint complex (MCC), the effector of the SAC. This attenuates MCC-mediated suppression of APC/C activity, allowing for more efficient ubiquitination of APC/C substrates in the presence of the MCC. Thus, SUMOylation stimulates the reactivation of APC/C when the SAC is silenced, contributing to timely anaphase onset.
External linksCell Rep / PubMed:33789095 / PubMed Central
MethodsEM (single particle)
Resolution3.78 - 3.99 Å
Structure data

10536

6tnt

EMDB-10536, PDB-6tnt:
SUMOylated apoAPC/C with repositioned APC2 WHB domain
Method: EM (single particle) / Resolution: 3.78 Å

EMDB-10538:
SUMOylated apoAPC/C with density at APC2-APC4 interface
Method: EM (single particle) / Resolution: 3.99 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • unidentified (others)
KeywordsCELL CYCLE / APC/C / APC2 / WHB domain / SUMOylation

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