A role for Ebi in neuronal cell cycle control.
Mutations in ebi were isolated as enhancers of an over-proliferation phenotype generated by elevated E2F/DP activity in the Drosophila eye. ebi alleles also strongly suppress a phenotype caused by the cyclin-dependent kinase inhibitor p21, restoring S phases in the second mitotic wave of the developing eye disk. ebi mutant embryos display ectopic S phases within the peripheral nervous system and central nervous system at a time in development when neuronal precursor cells would normally begin to differentiate. Consistent with this, we find that ebi mutants have a reduced capacity to undergo neuronal differentiation, that Ebi physically interacts with Sina and phyllopod, and that Ebi promotes Ttk88 degradation in vitro and in S2 cells. Ectopic expression of Ttk88 inhibited differentiation in embryos and eye discs; however, this block to differentiation was insufficient to promote S phase entry in either of the situations where ebi mutations gave this effect. We conclude that Ebi has two distinct functions; it promotes the degradation of a repressor of neuronal differentiation (Ttk88), and has a second independent function that limits S phase entry.
Boulton
S J
SJ
MGH Cancer Center, Laboratory of Molecular Oncology and Department of Pathology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Brook
A
A
Staehling-Hampton
K
K
Heitzler
P
P
Dyson
N
N
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology* / Q000235:genetics; D050703:E2F2 Transcription Factor; D005123:Eye / Q000196:embryology* / Q000648:ultrastructure; D019204:GTP-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009420:Nervous System / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D016415:Sequence Alignment; D013489:Suppression, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C115434:E2f2 protein, Drosophila; D019476:Insect Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014452:Ubiquitins; C119014:ebi protein, Drosophila; C075878:ttk protein, Drosophila; D019204:GTP-Binding Proteins