A role for Ebi in neuronal cell cycle control

Abstract

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.

Basolateral Junctions Utilize Warts Signaling to Control Epithelial-Mesenchymal Transition and Proliferation Crucial For Migration and Invasion of Drosophila Ovarian Epithelial Cells

“…The failure of ebi overexpression to suppress Fas2 or dlg, and the relatively mild ebi phenotypes (midoogenesis small-nucleus and epithelial-organization defects, but no defects in germinal vesicle localization), suggest that ebi may function in only one of the three branches of BLJ signaling ( Figure 1A) or in a parallel pathway to the BLJ. In the eye, ebi is important for promoting differentiation and inhibiting proliferation, which appear to be separable functions (Boulton et al 2000). Thus ebi could enhance Fas2 and dlg tumorigenesis by functioning within the proliferationrepressing branch of the BLJ, or the importance of ebi for differentiation suggests that it could function in the EMT branch of the BLJ ( Figure 1A) or both.…”

“…In addition, overexpression of all enhancers except ebi suppressed dlg and Fas2 tumorigenesis ( Figures 3C and 4D), further confirming that the identified genes function in a BLJ network. BLJ pathway components in the nucleus and their putative relationship to Notch: ebi encodes an F-box protein with WD repeats that promotes protein degradation of specific targets (Dong et al 1999;Boulton et al 2000). The failure of ebi overexpression to suppress Fas2 or dlg, and the relatively mild ebi phenotypes (midoogenesis small-nucleus and epithelial-organization defects, but no defects in germinal vesicle localization), suggest that ebi may function in only one of the three branches of BLJ signaling ( Figure 1A) or in a parallel pathway to the BLJ.…”

“…Thus ebi could enhance Fas2 and dlg tumorigenesis by functioning within the proliferationrepressing branch of the BLJ, or the importance of ebi for differentiation suggests that it could function in the EMT branch of the BLJ ( Figure 1A) or both. On the other hand, ebi promotes protein degradation in response to Notch (N) and Drosophila EGF receptor (EgfR) signals (Dong et al 1999;Boulton et al 2000;Tsuda et al 2002), suggesting that it may act in a parallel pathway. Both Ebi and its mammalian homolog, TBL1, function in a corepressor complex through association with nuclear hormone transcriptional corepressor SMRTER/SMRT (Guenther et al 2000;Tsuda et al 2002).…”

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners

“…Similarly, the F-box containing protein Ebi is specifically enriched in the BioTag sample. For example, Ebi is involved in substrate selection for E3-dependent proteasomal degradation during neuronal differentiation (25). To verify the suggested physical interactions, we performed genetic validation experiments.…”

Signal integration during development: Insights from the Drosophila eye

“…As described above, activation of Notch prevents R7 from assuming the R1/R6 fate. One important function of RTKs in the presumptive R7 is to activate an E3 Ligase complex composed of Seven in absentia (Sina), Phyllopod (Phyl), and Ebi (Li et al, 1997;Tang et al, 1997;Dong et al, 1999;Boulton et al, 2000;Li et al, 2002). This E3 complex ubiquitinates Tramtrack88 (Ttk88), a transcriptional repressor, targeting it for proteolysis.…”