Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles.
We demonstrate that fizzy-related (fzr), a conserved eukaryotic gene, negatively regulates the levels of cyclins A, B, and B3. These mitotic cyclins that bind and activate cdk1(cdc2) are rapidly degraded during exit from M and during G1. While Drosophila fizzy has previously been shown to be required for cyclin destruction during M phase, fzr is required for cyclin removal during G1 when the embryonic epidermal cell proliferation stops and during G2 preceding salivary gland endoreduplication. Loss of fzr causes progression through an extra division cycle in the epidermis and inhibition of endoreduplication in the salivary gland, in addition to failure of cyclin removal. Conversely, premature fzr overexpression down-regulates mitotic cyclins, inhibits mitosis, and transforms mitotic cycles into endoreduplication cycles.
Sigrist
S J
SJ
Department of Genetics, University of Bayreuth, Federal Republic of Germany.
Lehner
C F
CF
D000595:Amino Acid Sequence; D000818:Animals; D042846:CDC2-CDC28 Kinases; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology; D002455:Cell Division; D019926:Cyclin B; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology; D004705:Endocytosis; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D008938:Mitosis; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D014981:Xenopus; D029867:Xenopus Proteins
D064199:Cdc20 Proteins; C577501:Cdc20 protein, Xenopus; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C503698:CycB protein, Drosophila; D019926:Cyclin B; D016213:Cyclins; D029721:Drosophila Proteins; D019476:Insect Proteins; D029867:Xenopus Proteins; C577674:fzr protein, Drosophila; C577588:fzr1 protein, Xenopus; C577502:fzy protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila