The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis.
Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac-Tramtrack-Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to aurora B and mediates ubiquitination of aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B at distinct subcellular localizations.
Maerki
Sarah
S
Institute of Biochemistry, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland.
Olma
Michael H
MH
Staubli
Titu
T
Steigemann
Patrick
P
Gerlich
Daniel W
DW
Quadroni
Manfredo
M
Sumara
Izabela
I
Peter
Matthias
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000705:Anaphase / Q000235:genetics; D064107:Aurora Kinase B; D064127:Aurora Kinases; D020090:Chromosome Segregation; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000201:enzymology*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; C503645:CUL3 protein, human; D044842:Cullin Proteins; C586714:KLHL22 protein, human; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D044767:Ubiquitin-Protein Ligases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases