Abstract

Both mind bomb ( mib) and mind bomb-2 ( mib2) encode RING E3 ubiquitin ligases that promote Delta ubiquitylation and endocytosis in Notch activation. Detailed morphological and molecular examinations revealed that zebrafish mib ta52b (missense mutation in the C-terminal RING Finger (RF), M1013R) and mib m132 (nonsense mutation resulting in a truncated protein that loses all three RFs, C785stop) are strong and weak antimorphic alleles, respectively, compared to the null allele, mib tfi91 (nonsense mutation resulting in a truncated protein of only 60 amino acids, Y60stop). Zebrafish mib2 ortholog was identified in this study. Zebrafish Mib and Mib2 are colocalized in transfected cells and function redundantly in regulating Notch signaling in embryos. Mib ta52b and Mib m132 have a dosage-dependent dominant-negative effect, at least, on Mib2, which is a molecular basis for the antimorphic phenotypes. It was also shown that Notch signaling negatively regulates mib expression in a Su(H)-dependent manner, forming a negative feedback loop in modulating Notch activation.

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