Mitotic destruction of the cell cycle regulated NIMA protein kinase of Aspergillus nidulans is required for mitotic exit.
NIMA is a cell cycle regulated protein kinase required, in addition to p34cdc2/cyclin B, for initiation of mitosis in Aspergillus nidulans. Like cyclin B, NIMA accumulates when cells are arrested in G2 and is degraded as cells traverse mitosis. However, it is stable in cells arrested in mitosis. NIMA, and related kinases, have an N-terminal kinase domain and a C-terminal extension. Deletion of the C-terminus does not completely inactivate NIMA kinase activity but does prevent functional complementation of a temperature sensitive mutation of nimA, showing it to be essential for function. Partial C-terminal deletion of NIMA generates a highly toxic kinase although the kinase domain alone is not toxic. Transient induction experiments demonstrate that the partially truncated NIMA is far more stable than the full length NIMA protein which likely accounts for its toxicity. Unlike full length NIMA, the truncated NIMA is not degraded during mitosis and this affects normal mitotic progression. Cells arrested in mitosis with non-degradable NIMA are able to destroy cyclin B, demonstrating that the arrest is not due to stabilization of p34cdc2/cyclin B activity. The data establish that NIMA degradation during mitosis is required for correct mitotic progression in A. nidulans.
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Weis Center for Research, Geisinger Clinic, Danville, PA 17822-2617.
Osmani
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D001233:Aspergillus nidulans / Q000166:cytology / Q000201:enzymology*; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000502:physiology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000378:metabolism; D004790:Enzyme Induction; D004795:Enzyme Stability; D004926:Escherichia coli / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D005816:Genetic Complementation Test; D008938:Mitosis; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion / Q000502:physiology
D018797:Cell Cycle Proteins; D016213:Cyclins; D011994:Recombinant Proteins; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase