Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The anaphase-promoting complex/cyclosome (
APC
/C) ubiquitin ligase is known to target the degradation of cyclin B1, which is crucial for mitotic progression in animal cells. In this study, we show that the ubiquitin ligase CRL2
ZYG-11
redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. In C. elegans, both CRL2
ZYG-11
and
APC
/C are required for proper progression through meiotic divisions. In human cells, inactivation of CRL2
ZYG11A
/B
has minimal effects on mitotic progression when
APC
/C is active. However, when
APC
/C is inactivated or cyclin B1 is overexpressed, CRL2
ZYG11A
/B
-mediated degradation of cyclin B1 is required for normal progression through metaphase. Mitotic cells arrested by the spindle assembly checkpoint, which inactivates
APC
/C, often exit mitosis in a process termed "mitotic slippage," which generates tetraploid cells and limits the effectiveness of antimitotic chemotherapy drugs. We show that
ZYG11A
/B subunit knockdown, or broad cullin-RING ubiquitin ligase inactivation with the small molecule MLN4924, inhibits mitotic slippage in human cells, suggesting the potential for antimitotic combination therapy.
...
PMID:The ubiquitin ligase CRL2ZYG11 targets cyclin B1 for degradation in a conserved pathway that facilitates mitotic slippage. 2781 Sep 9
