Regulation of the anaphase-promoting complex/cyclosome by bimAAPC3 and proteolysis of NIMA.
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 + 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 bimAAPC3 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 bimAAPC3 regulates the APC/C in a NIMA-dependent manner.
Ye
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Henry Hood Research Program, Weis Center for Research, Pennsylvania State University College of Medicine, Danville, Pennsylvania 17822, USA.
Fincher
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RR
Tang
A
A
Osmani
A H
AH
Osmani
S A
SA
D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D008025:Ligases / Q000378:metabolism*; D008938:Mitosis; D016296:Mutagenesis; D009154:Mutation; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
C065697:BIME protein, Emericella nidulans; D018797:Cell Cycle Proteins; D016213:Cyclins; D005656:Fungal Proteins; D009687:Nuclear Proteins; C072411:BIMA protein, Emericella nidulans; C075058:NIME protein, Emericella nidulans; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D010450:Endopeptidases; D008025:Ligases