Fission Yeast Slp1: An Effector of the Mad2-Dependent Spindle Checkpoint

Kim, Sang Hoon; Lin, Diana P.; Matsumoto, Sanae; Kitazono, Ana; Matsumoto, Tomohiro

doi:10.1126/science.279.5353.1045

Cited by 357 publications

(317 citation statements)

References 27 publications

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“…Although fission yeast Mph1p is the structural and functional homologue of budding yeast Mps1p [He et al, 1998;reviewed in Winey and Huneycutt, 2002], Mph1p is not essential for viability or spindle pole body duplication in fission yeast [He et al, 1998]. Fission yeast Mad2p was also independently identified based on its interaction with an activator of the Anaphase Promoting Complex/Cyclosome (APC/C), Slp1p [Kim et al, 1998], which is called Cdc20p in budding yeast and animal cells. S. pombe Mad1p, Mad3p, Bub1p, and Bub3p were identified based on their amino acid sequence similarity to S. cerevisiae proteins [Bernard et al, 1998;Ikui et al, 2002;Kim et al, 2003;.…”

Section: Fission Yeastmentioning

confidence: 99%

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Kadura

Sazer

2005

Cell Motil. Cytoskeleton

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Section: Fission Yeastmentioning

confidence: 99%

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Kadura

Sazer

2005

Cell Motil. Cytoskeleton

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“…Several regulators of the APC/cyclosome have been identi®ed. They include protein kinase A (Yamashita et al 1996 and spindle checkpoint-related Slp1 (Kim et al 1998).…”

Section: Fission Yeast Cut2/securin Degrades In Anaphasementioning

confidence: 99%

Cell cycle mechanisms of sister chromatid separation; Roles of Cut1/separin and Cut2/securin

Yanagida

2000

Genes to Cells

103

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The correct transmission of chromosomes from mother to daughter cells is fundamental for genetic inheritance. Separation and segregation of sister chromatids in growing cells occurs in the cell cycle stage called`anaphase'. The basic process of sister chromatid separation is similar in all eukaryotes: many gene products required are conserved. In this review, the roles of two proteins essential for the onset of anaphase in ®ssion yeast, Cut2/securin and Cut1/separin, are discussed with regard to cell cycle regulation, and compared with the postulated roles of homologous proteins in other organisms. Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. The anaphase never occurs properly in the absence of securin destruction. In human cells, securin is an oncogene. Separin is a large protein (MW <180 kDa), the C-terminus of which is conserved, and is thought to be inhibited by association with securin at the nonconserved N-terminus. In the budding yeast, Esp1/separin is thought to be a component of proteolysis against Scc1, an essential subunit of cohesin which is thought to link duplicated sister chromatids up to the anaphase. Whether ®ssion yeast Cut1/separin is also implicated in proteolysis of cohesin is discussed.

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“…APC bound with Cdc20 targets Pds1, whereas the APCCdh1 complex recognizes cyclin B (Visintin et al, 1997). When the spindle checkpoint is activated, Mad2 probably binds and inhibits Cdc20 (Fang et al, 1998;Hwang et al, 1998;Kim et al, 1998), thus preventing Pds1 degradation and sister chromatid segregation. BubR1 has also been shown recently to have a similar inhibitory effect on APC Cdc20 in vitro (Tang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Spindle Checkpoint Requires Mad1-bound and Mad1-free Mad2

Chung

Chen

2002

MBoC

120

136

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The spindle checkpoint prevents anaphase from occurring until all chromosomes have attached properly to the mitotic spindle. The checkpoint components Mad1 and Mad2 associate with unattached kinetochores and are probably involved in triggering the checkpoint. We now demonstrate that in Xenopus egg extracts Mad1 and Mad2 form a stable complex, whereas a fraction of Mad2 molecules is not bound to Mad1. The checkpoint establishment and maintenance are lost upon titrating out free Mad2 with an excess of Mad1 or a truncated Mad1 (amino acids 326 -718, Mad1C) that contains the Mad2-binding region. Mad1N (amino acids 1-445) that binds kinetochores, but not Mad2, reduces Mad1 and Mad2 at kinetochores and abolishes checkpoint maintenance. Furthermore, the association between Mad2 and Cdc20, the activator for the anaphasepromoting complex, is enhanced under checkpoint-active condition compared with that at metaphase. Immunodepletion analysis shows that the Mad1-free Mad2 protein is unable to bind Cdc20, consistent with the model that kinetochore localization of Mad2 facilitates the formation of Mad2-Cdc20 complex. This study demonstrates that the ratio between Mad1 and Mad2 is critical for maintaining a pool of Mad1-free Mad2 that is necessary for the spindle checkpoint. We propose that Mad2 may become activated and dissociated from Mad1 at kinetochores and is replenished by the pool of Mad1-free Mad2.

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Fission Yeast Slp1: An Effector of the Mad2-Dependent Spindle Checkpoint

Cited by 357 publications

References 27 publications

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Cell cycle mechanisms of sister chromatid separation; Roles of Cut1/separin and Cut2/securin

Spindle Checkpoint Requires Mad1-bound and Mad1-free Mad2

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