Degradation of Drosophila PIM regulates sister chromatid separation during mitosis.
Drosophila Pimples (PIM) and Three rows (THR) are required for sister chromatid separation in mitosis. PIM accumulates during interphase and is degraded rapidly during mitosis. This degradation is dependent on a destruction box similar to that of B-type cyclins. Nondegradable PIM with a mutant destruction box can rescue sister chromatid separation in pim mutants but only when expressed at low levels. Higher levels of nondegradable PIM, as well as overexpression of wild-type PIM, inhibit sister chromatid separation. Moreover, cells arrested in mitosis before sister chromatid separation (by colcemid or by mutations in fizzy/CDC20) fail to degrade PIM. Thus, although not related by primary sequence, PIM has intriguing functional similarities to the securin proteins of budding yeast, fission yeast, and vertebrates. Whereas these securins are known to form a complex with separins, we show that PIM associates in vivo with THR, which does not contain the conserved separin domain.
Leismann
O
O
Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany.
Herzig
A
A
Heidmann
S
S
Lehner
C F
CF
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids / Q000235:genetics* / Q000648:ultrastructure; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D003703:Demecolcine / Q000494:pharmacology; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D000939:Epitopes; D005656:Fungal Proteins / Q000378:metabolism; D015151:Immunoblotting; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C503698:CycB protein, Drosophila; D019926:Cyclin B; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D000939:Epitopes; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D019476:Insect Proteins; C413708:PIM protein, Drosophila; D016271:Proto-Oncogene Proteins c-myc; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C577502:fzy protein, Drosophila; C085015:thr protein, Drosophila; D003703:Demecolcine