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Wild, Thomas ; Budzowska, Magda ; Hellmuth, Susanne ; Eibes, Susana ; Karemore, Gopal ; Barisic, Marin ; Stemmann, Olaf ; Choudhary, Chunaram:
Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint.
In: Cell Reports.
Bd. 25
(2018)
Heft 9
.
- S. 2317-2328.
ISSN 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2018.10.104
Abstract
The multisubunit ubiquitin ligase APC/C (anapha sepromoting complex/cyclosome) is essential for mitosis by promoting timely degradation of cyclin B1. APC/C is tightly regulated by the spindle assembly checkpoint (SAC), which involves MPS1 and MAD2-dependent temporal inhibition of APC/C. We analyzed the contribution of the APC/C subunits APC7 and APC16 to APC/C composition and function in human cells. APC16 is required for APC7 assembly into APC/C, whereas APC16 assembles independently of APC7. APC7 and APC16 knockout cells display no major defects in mitotic progression, cyclin B1 degradation, or SAC response, but APC/C lacking these two subunits shows reduced ubiquitylation activity in vitro. Strikingly, deletion of APC7 or APC16 is sufficient to provide synthetic viability to MAD2 deletion. Delta APC7DMAD2 cells display accelerated mitosis and require SAC-independent MPS1 function for genome stability. These findings reveal that the composition of APC/C critically influences the importance of the SAC in humans.
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| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Keywords: | ANAPHASE-PROMOTING COMPLEX; CHROMOSOME INSTABILITY; UBIQUITIN CHAINS; DEGRADATION; CYCLIN; MAD2; MPS1 |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Biologie > Lehrstuhl Genetik > Lehrstuhl Genetik - Univ.-Prof. Dr. Olaf Stemmann Fakultäten Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Biologie Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Biologie > Lehrstuhl Genetik |
| Titel an der UBT entstanden: | Ja |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| Eingestellt am: | 26 Feb 2020 09:20 |
| Letzte Änderung: | 19 Okt 2022 11:46 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/54403 |