The C-terminal disordered loop domain of Apc8 unlocks APC/C mitotic activation.
Cell Rep
; 43(6): 114262, 2024 Jun 25.
Article
in En
| MEDLINE
| ID: mdl-38776225
ABSTRACT
The anaphase-promoting complex/cyclosome (APC/C) is a critical and tightly regulated E3 ligase that orchestrates the cellular life cycle by controlling the degradation of cell cycle regulators. An intriguing feature of this complex is an autoinhibition mechanism an intrinsically disordered loop domain, Apc1-300L, blocks Cdc20 coactivator binding, yet phosphorylation of Apc1-300L counteracts this autoinhibition. Many such disordered loops within APC/C remain unexplored. Our systematic analysis of loop-deficient APC/C mutants uncovered a pivotal role for Apc8's C-terminal loop (Apc8-L) in mitotic activation. Apc8-L directly recruits the CDK adaptor protein, Xe-p9/Cks2, positioning the Xe-p9-CDK-CycB complex near Apc1-300L. This stimulates the phosphorylation and removal of Apc1-300L, prompting the formation of active APC/CCdc20. Strikingly, without both Apc8-L and Apc3-L, the APC/C is rendered inactive during mitosis, highlighting Apc8-L's synergistic role with other loops and kinases. This study broadens our understanding of the intricate dynamics in APC/C regulation and provides insights on the regulation of macromolecular complexes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitosis
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
Reino Unido
Country of publication:
Estados Unidos