Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B.
Accurate chromosome segregation relies on the mitotic spindle checkpoint. This checkpoint acts to restrict ubiquitin ligase activity of the Anaphase-promoting complex (APC/C) in mitosis until all chromosomes are bipolarly attached to the mitotic spindle. We performed a functional RNAi-based screen to identify De-ubiquitinating enzymes (Dubs) involved in mitotic progression. We identified Usp39 as a new factor required to maintain the spindle checkpoint and support successful cytokinesis. Strikingly, although Usp39 clearly contains an ubiquitin-protease domain, we show that Usp39 is entirely deprived of Dub activity. However, consistent wilt a previously described role for Usp39 in mRNA processing, we observed specific reduction in Aurora B-mRNA levels after depletion of Usp39. Although we find that exogenously expressed Aurora B cDNA is not sufficient to rescue the checkpoint defect of Usp39-depleted cells, Aurora B expression is restored. Our observations suggest Usp39 to be involved in splicing of Aurora B and other mRNAs that are essential for proper spindle checkpoint function.
van Leuken
Renske J
RJ
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Luna-Vargas
Mark P
MP
Sixma
Titia K
TK
Wolthuis
Rob M F
RM
Medema
René H
RH
D000595:Amino Acid Sequence; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002384:Catalysis / Q000187:drug effects; D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000201:enzymology*; D064570:Ubiquitin-Specific Proteases
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases; C579218:USP39 protein, human; D064570:Ubiquitin-Specific Proteases; D017239:Paclitaxel