Faculty Opinions recommendation of S. pombe cdc11p, together with sid4p, provides an anchor for septation initiation network proteins on the spindle pole body.

In Schizosaccharomyces pombe, late mitotic events are coordinated with cytokinesis by the septation initiation network (SIN), an essential spindle pole body (SPB)–associated kinase cascade, which controls the formation, maintenance, and constriction of the cytokinetic ring. It is not fully understood how SIN initiation is temporally regulated, but it depends on the activation of the GTPase Spg1, which is inhibited during interphase by the essential bipartite GTPase-activating protein Byr4-Cdc16. Cells are particularly sensitive to the modulation of Byr4, which undergoes cell cycle–dependent phosphorylation presumed to regulate its function. Polo-like kinase, which promotes SIN activation, is partially responsible for Byr4 phosphorylation. Here we show that Byr4 is also controlled by cyclin-dependent kinase (Cdk1)–mediated phosphorylation. A Cdk1 nonphosphorylatable Byr4 phosphomutant displays severe cell division defects, including the formation of elongated, multinucleate cells, failure to maintain the cytokinetic ring, and compromised SPB association of the SIN kinase Cdc7. Our analyses show that Cdk1-mediated phosphoregulation of Byr4 facilitates complete removal of Byr4 from metaphase SPBs in concert with Plo1, revealing an unexpected role for Cdk1 in promoting cytokinesis through activation of the SIN pathway.

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S. pombe cdc11p, together with sid4p, provides an anchor for septation initiation network proteins on the spindle pole body

Current Biology ◽

10.1016/s0960-9822(01)00478-x ◽

2001 ◽

Vol 11 (20) ◽

pp. 1559-1568 ◽

Cited By ~ 62

Author(s):

Andrea Krapp ◽

Susanne Schmidt ◽

Elena Cano ◽

Viesturs Simanis

Keyword(s):

Spindle Pole Body ◽

Spindle Pole ◽

Pole Body ◽

Septation Initiation Network

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Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization

Molecular Biology of the Cell ◽

10.1091/mbc.e18-04-0261 ◽

2018 ◽

Vol 29 (18) ◽

pp. 2176-2189 ◽

Cited By ~ 1

Author(s):

Christine M. Jones ◽

Jun-Song Chen ◽

Alyssa E. Johnson ◽

Zachary C. Elmore ◽

Sierra N. Cullati ◽

...

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Ubiquitin Ligase ◽

Spindle Pole Body ◽

Mitotic Checkpoint ◽

Spindle Pole ◽

Checkpoint Activation ◽

Pole Body ◽

Septation Initiation Network ◽

Anaphase B

Chromosome segregation and cell division are coupled to prevent aneuploidy and cell death. In the fission yeast Schizosaccharomyces pombe, the septation initiation network (SIN) promotes cytokinesis, but upon mitotic checkpoint activation, the SIN is actively inhibited to prevent cytokinesis from occurring before chromosomes have safely segregated. SIN inhibition during the mitotic checkpoint is mediated by the E3 ubiquitin ligase Dma1. Dma1 binds to the CK1-phosphorylated SIN scaffold protein Sid4 at the spindle pole body (SPB), and ubiquitinates it. Sid4 ubiquitination antagonizes the SPB localization of the Pololike kinase Plo1, the major SIN activator, so that SIN signaling is delayed. How this checkpoint is silenced once spindle defects are resolved has not been clear. Here we establish that Dma1 transiently leaves SPBs during anaphase B due to extensive autoubiquitination. The SIN is required for Dma1 to return to SPBs later in anaphase. Blocking Dma1 removal from SPBs by permanently tethering it to Sid4 prevents SIN activation and cytokinesis. Therefore, controlling Dma1’s SPB dynamics in anaphase is an essential step in S. pombe cell division and the silencing of the Dma1-dependent mitotic checkpoint.

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Ppc89 Links Multiple Proteins, Including the Septation Initiation Network, to the Core of the Fission Yeast Spindle-Pole Body

Molecular Biology of the Cell ◽

10.1091/mbc.e06-01-0039 ◽

2006 ◽

Vol 17 (9) ◽

pp. 3793-3805 ◽

Cited By ~ 36

Author(s):

Joshua A. Rosenberg ◽

Gregory C. Tomlin ◽

W. Hayes McDonald ◽

Brian E. Snydsman ◽

Eric G. Muller ◽

...

Keyword(s):

Chromosome Segregation ◽

Spindle Pole Body ◽

Spindle Pole ◽

Uncharacterized Protein ◽

Central Function ◽

Pole Body ◽

Organizing Center ◽

Septation Initiation Network ◽

Ring Constriction ◽

Essential Function

The spindle-pole body (SPB), the yeast analog of the centrosome, serves as the major microtubule (MT) organizing center in the yeast cell. In addition to this central function, the SPB organizes and concentrates proteins required for proper coordination between the nuclear-division cycle and cytokinesis. For example, the Schizosaccharomyces pombe septation-initiation network (SIN), which is responsible for initiating actomyosin ring constriction and septation, is assembled at the SPB through its two scaffolding components, Sid4 and Cdc11. In an effort to identify novel SIN interactors, we purified Cdc11 and identified by mass spectrometry a previously uncharacterized protein associated with it, Ppc89. Ppc89 localizes constitutively to the SPB and interacts directly with Sid4. A fusion between the N-terminal 300 amino acids of Sid4 and a SPB targeting domain of Ppc89 supplies the essential function of Sid4 in anchoring the SIN. ppc89Δ cells are inviable and exhibit defects in SPB integrity, and hence in spindle formation, chromosome segregation, and SIN localization. Ppc89 overproduction is lethal, resulting primarily in a G2 arrest accompanied by massive enlargement of the SPB and increased SPB MT nucleation. These results suggest a fundamental role for Ppc89 in organization of the S. pombe SPB.

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The Spindle Pole Body Protein Cdc11p Links Sid4p to the Fission Yeast Septation Initiation Network

Molecular Biology of the Cell ◽

10.1091/mbc.01-09-0455 ◽

2002 ◽

Vol 13 (4) ◽

pp. 1203-1214 ◽

Cited By ~ 57

Author(s):

Gregory C. Tomlin ◽

Jennifer L. Morrell ◽

Kathleen L. Gould

Keyword(s):

Spindle Pole Body ◽

Direct Interaction ◽

Spindle Pole ◽

Small Gtpase ◽

Dependent Manner ◽

Body Protein ◽

Pole Body ◽

C Terminus ◽

N Terminus ◽

Septation Initiation Network

The Schizosaccharomyces pombe septation initiation network (SIN) signals the onset of cell division from the spindle pole body (SPB) and is regulated by the small GTPase Spg1p. The localization of SIN components including Spg1p to the SPB is required for cytokinesis and is dependent on Sid4p, a constitutive resident of SPBs. However, a direct interaction between Sid4p and other members of the SIN has not been detected. To understand how Sid4p is linked to other SIN components, we have begun to characterize an S. pombe homolog of the Saccharomyces cerevisiaeSPB protein Nud1p. We have determined that this S. pombeNud1p homolog corresponds to Cdc11p, a previously uncharacterized SIN element. We report that Cdc11p is present constitutively at SPBs and that its function appears to be required for the localization of all other SIN components to SPBs with the exception of Sid4p. The Cdc11p C terminus localizes the protein to SPBs in a Sid4p-dependent manner, and we demonstrate a direct Cdc11p-Sid4p interaction. The N-terminus of Cdc11p is required for Spg1p binding to SPBs. Our studies indicate that Cdc11p provides a physical link between Sid4p and the Spg1p signaling pathway.

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Timely Septation Requires SNAD-dependent Spindle Pole Body Localization of the Septation Initiation Network Components in the Filamentous FungusAspergillus nidulans

Molecular Biology of the Cell ◽

10.1091/mbc.e08-12-1177 ◽

2009 ◽

Vol 20 (12) ◽

pp. 2874-2884 ◽

Cited By ~ 31

Author(s):

Jung-Mi Kim ◽

Cui Jing Tracy Zeng ◽

Tania Nayak ◽

Rongzhong Shao ◽

An-Chi Huang ◽

...

Keyword(s):

Spindle Pole Body ◽

Coiled Coil ◽

Spindle Pole ◽

Scaffold Protein ◽

Negative Regulators ◽

Timely Manner ◽

Division Site ◽

Pole Body ◽

Septation Initiation Network ◽

Per Se

In the filamentous fungus Aspergillus nidulans, cytokinesis/septation is triggered by the septation initiation network (SIN), which first appears at the spindle pole body (SPB) during mitosis. The coiled-coil protein SNAD is associated with the SPB and is required for timely septation and conidiation. We have determined that SNAD acted as a scaffold protein that is required for the localization of the SIN proteins of SIDB and MOBA to the SPB. Another scaffold protein SEPK, whose localization at the SPB was dependent on SNAD, was also required for SIDB and MOBA localization to the SPB. In the absence of either SEPK or SNAD, SIDB/MOBA successfully localized to the septation site, indicating that their earlier localization at SPB was not essential for their later appearance at the division site. Unlike their functional counterparts in fission yeast, SEPK and SNAD were not required for vegetative growth but only for timely septation. Furthermore, down-regulation of negative regulators of the SIN suppressed the septation and conidiation phenotypes due to the loss of SNAD. Therefore, we conclude that SPB localization of SIN components is not essential for septation per se, but critical for septation to take place in a timely manner in A. nidulans.

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