CK1 is required for a mitotic checkpoint that delays cytokinesis.
Failure to accurately partition genetic material during cell division causes aneuploidy and drives tumorigenesis. Cell-cycle checkpoints safeguard cells from such catastrophes by impeding cell-cycle progression when mistakes arise. FHA-RING E3 ligases, including human RNF8 and CHFR and fission yeast Dma1, relay checkpoint signals by binding phosphorylated proteins via their FHA domains and promoting ubiquitination of downstream targets. Upon mitotic checkpoint activation, S. pombe Dma1 concentrates at spindle pole bodies (SPBs) in an FHA-dependent manner and ubiquitinates Sid4, a scaffold of Polo kinase, to suspend cytokinesis. However, the kinase or kinases that phosphoprime Sid4 for Dma1-mediated ubiquitination are unknown. Here, we report that the highly conserved protein kinase CK1 transmits the signal necessary to stall cytokinesis by phosphopriming Sid4 for Dma1-mediated ubiquitination. Like Dma1, CK1 accumulates at SPBs during a mitotic arrest and associates stably with SPB components, including Sid4. Our results establish CK1 as an integral component of a mitotic, ubiquitin-mediated checkpoint pathway.
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Alyssa E
AE
Johnson
Jun-Song
JS
Chen
Kathleen L
KL
Gould
D047389:Casein Kinase I / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D059566:M Phase Cell Cycle Checkpoints; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D064048:Spindle Pole Bodies / Q000378:metabolism; D054875:Ubiquitination
C544653:Bub3 protein, S pombe; D018797:Cell Cycle Proteins; C103134:Dma1 protein, S pombe; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C409024:Sid4 protein, S pombe; C498281:cdc16 protein, S pombe; C501383:mad1 protein, S pombe; D049452:Green Fluorescent Proteins; C570446:Mph1 protein, S pombe; D011494:Protein Kinases; C088232:hhp1 protein, S pombe; C088231:hhp2 protein, S pombe; C495594:Bub1 protein, S pombe; D047389:Casein Kinase I; D017346:Protein Serine-Threonine Kinases