Examining the mechanistic relationship of APC/CCDH1 and its interphase inhibitor EMI1.
Protein Sci
; 31(6): e4324, 2022 06.
Article
in En
| MEDLINE
| ID: mdl-35634770
ABSTRACT
Proper protein destruction by the ubiquitin (Ub)-proteasome system is vital for a faithful cell cycle. Hence, the activity of Ub ligases is tightly controlled. The Anaphase-Promoting Complex/Cyclosome (APC/C) is a 1.2 MDa Ub ligase responsible for mitotic progression and G1 maintenance. At the G1/S transition, the APC/C is inhibited by EMI1 to prevent APC/C-dependent polyubiquitination of cell cycle effectors. EMI1 uses several interaction motifs to block the recruitment of APC/C substrates as well as the APC/C-associated E2s, UBE2C, and UBE2S. Paradoxically, EMI1 is also an APC/C substrate during G1. Using a comprehensive set of enzyme assays, we determined the context-dependent involvement of the EMI1 motifs in APC/C-dependent ubiquitination of EMI1 and other substrates. Furthermore, we demonstrated that an isolated C-terminal peptide fragment of EMI1 activates APC/C-dependent substrate priming by UBE2C. Together, these findings reveal the multiple roles of the EMI1 C-terminus for G1 maintenance and the G1/S transition.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
F-Box Proteins
Language:
En
Journal:
Protein Sci
Journal subject:
BIOQUIMICA
Year:
2022
Type:
Article
Affiliation country:
United States