Cut2 proteolysis required for sister-chromatid separation in fission yeast

Funabiki, Hironori; Yamano, Hiroyuki; Kumada, Kazuki; Nagao, Koji; Hunt, Tim; Yanagida, Mitsuhiro

doi:10.1038/381438a0

Cited by 443 publications

(388 citation statements)

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“…Additionally, the presence of higher than normal levels of mE2-C during mitosis could lead to increases in the rates of ubiquitin-dependent proteolysis of both mitotic cyclins as shown here, and in the destruction of other proteins that regulate anaphase onset and sister chromosome separation later in mitosis (Cohen et al, 1996;Funabiki et al, 1996;Guacci et al, 1997;Juang et al, 1997;Michaelis et al, 1997;Stratmann et al, 1996). Imbalances in the rates of these normally coordinated processes could contribute to conditions that promote aneuploidy.…”

Section: Discussionmentioning

confidence: 72%

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

et al. 1998

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The EWS/FLI1 fusion gene found in Ewing's sarcoma and primitive neuroectodermal tumor, is able to transform certain cell lines by acting as an aberrant transcription factor. The ability of EWS/FLI1 to modulate gene expression in cells transformed and resistant to transformation by EWS/FLI1, was assessed by Representational Di erence Analysis (RDA). We found that the cyclin selective ubiquitin conjugase murine E2-C, was up regulated in NIH3T3 cells transformed by EWS/FLI1 but not in a nontransformed NIH3T3 clone expressing EWS/FLI1. We also found that mE2-C is upregulated in NIH3T3 cells transformed by other genes including activated cdc42, v-ABL and c-myc. We demonstrated that expression of mE2-C in both the EWS/FLI1 transformed and parent NIH3T3 lines varies with the cell cycle. Finally, dominant-negative mE2-C, created by changing a catalytic cysteine to serine, inhibits the in vitro ubiquitination and degradation of cyclin B in human HeLa cell extracts. These data suggest that part of the biologic e ect of EWS/FLI1 could be to transcriptionally modulate genes involved in cell cycle regulation.

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Section: Discussionmentioning

confidence: 72%

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

et al. 1998

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“…Mitotic degradation of other regulatory proteins (Cohen-Fix et al, 1996;Funabiki et al, 1996;Juang et al, 1997;Michaelis et al, 1997;Charles et al, 1998;Shirayama et al, 1998) is also required for normal exit from mitosis, and these proteins are . 10, 13, 32, 76, 109, and 131 are deletions in GR5, and 19R and 30R indicate deletions in a bimE7 APC1 strain.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Anaphase-promoting Complex/Cyclosome bybimA^APC3and Proteolysis of NIMA

Fincher

Tang

et al. 1998

MBoC

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Surprisingly, although highly temperature-sensitive, the bimA1 APC3 anaphase-promoting complex/cyclosome (APC/C) mutation does not cause arrest of mitotic exit. Instead, rapid inactivation of bimA1 APC3 is shown to promote repeating oscillations of chromosome condensation and decondensation, activation and inactivation of NIMA and p34 cdc2 kinases, and accumulation and degradation of NIMA, which all coordinately cycle multiple times without causing nuclear division. These bimA1 APC3 -induced cell cycle oscillations require active NIMA, because a nimA5 ϩ bimA1 APC3 double mutant arrests in a mitotic state with very high p34 cdc2 H1 kinase activity. NIMA protein instability during S phase and G2 was also found to be controlled by the APC/C. The bimA1 APC3 mutation therefore first inactivates the APC/C but then allows its activation in a cyclic manner; these cycles depend on NIMA. We hypothesize that bimA APC3 could be part of a cell cycle clock mechanism that is reset after inactivation of bimA1 APC3 . The bimA1 APC3 mutation may also make the APC/C resistant to activation by mitotic substrates of the APC/C, such as cyclin B, Polo, and NIMA, causing mitotic delay. Once these regulators accumulate, they activate the APC/C, and cells exit from mitosis, which then allows this cycle to repeat. The data indicate that bimA APC3 regulates the APC/C in a NIMA-dependent manner. INTRODUCTIONThe bimE and bimA genes were originally defined by temperature-sensitive mutations in functions required for normal progression through mitosis in Aspergillus nidulans (Morris, 1976;Osmani et al., 1988;Engle et al., 1990;O'Donnell et al., 1991) and were subsequently found to encode highly conserved proteins whose homologues have been isolated from many organisms ranging from fungi to humans (Hirano et al., 1990(Hirano et al., , 1994Mirabito and Morris, 1993;Lamb et al., 1994;Starborg et al., 1994;King et al., 1995;. Most significantly, they were recently identified as components of the anaphase-promoting complex (APC) (King et al., 1995;Peters et al., 1996;. The APC is also known as the cyclosome and is therefore abbreviated here to APC/C (see Townsley and Ruderman, 1998, for review).bimE encodes the largest subunit of the APC/C and has recently been termed APC1 . We will use the designation bimE APC1 for the gene and BIME APC1 for the protein. bimA encodes a member of the tetratricopeptide repeat family of proteins, being most similar to Schizosaccharomyces pombe nuc2 (Hirano et al., 1990(Hirano et al., , 1994 and Saccharomyces cerevisiae CDC27 (Sikorski et al., 1990;Lamb et al., 1994), which was recently termed APC3 APC/C functions as an E3 ubiquitin ligase, which specifically targets proteins (such as mitotic cyclins) for degradation in a destruction box (D box)-dependent manner (Glotzer et al., 1991;King et al., 1996b) through the ubiquitin-proteasome pathway, to promote initiation of anaphase and exit from mitosis into G1 (for reviews see Murray, 1995;King et al., 1996a;Hershko, 1997;Townsley and Ruderman, 1998). APC/C activity i...

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“…By way of comparison, a top2 mutant cell which is defective in condensation and separation is shown (Uemura et al 1987). (Zou et al 1999;Nagase et al 1996) Yamada et al 1997) in a manner which resembles highly that of mitotic cyclins (Funabiki et al 1996a(Funabiki et al , 1997. The destruction modes of Cut2 and Cdc13 (a ®ssion yeast mitotic cyclin) are shown in Fig.…”

Section: Fission Yeast Cut2/securin Degrades In Anaphasementioning

confidence: 97%

“…Sequence similarity among securin in different organisms is low, except for the presence of destruction box sequences (see below) and the charge distribution (Zou et al 1999). Cut2 is a nuclear protein in postreplicative interphase cells, but enriched along the metaphase spindle, and rapidly degrades following the onset of anaphase (Funabiki et al 1996a). The level of Cut2 protein is rapidly restored during the S phase.…”

Section: Fission Yeast Cut2/securin Degrades In Anaphasementioning

confidence: 99%

“…Securin/Cut2/Pds1 degrade at the onset of anaphase in a manner that is very similar to the destruction of mitotic cyclins, the major regulator of the cell cycle, and this destruction is essential for sister chromatid separation (Cohen-Fix et al 1996;Funabiki et al 1996a). Vertebrate vSecurin is identical to the oncogene PTTG, and produces chromosome aberration when it is not degraded (Zou et al 1999).…”

Section: Introductionmentioning

confidence: 99%

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

Yanagida

2000

Genes to Cells

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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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Cut2 proteolysis required for sister-chromatid separation in fission yeast

Cited by 443 publications

References 27 publications

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

Regulation of the Anaphase-promoting Complex/Cyclosome bybimA^APC3and Proteolysis of NIMA

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

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Cut2 proteolysis required for sister-chromatid separation in fission yeast

Cited by 443 publications

References 27 publications

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

Regulation of the Anaphase-promoting Complex/Cyclosome bybimAAPC3and Proteolysis of NIMA

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

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Regulation of the Anaphase-promoting Complex/Cyclosome bybimA^APC3and Proteolysis of NIMA