The characterization of zebrafish antimorphic mib alleles reveals that Mib and Mind bomb-2 (Mib2) function redundantly.
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.
Zhang
Chengjin
C
Laboratory of Developmental Signalling and Patterning, Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, 138673, Singapore.
Li
Qing
Q
Lim
Chiaw-Hwee
CH
Qiu
Xuehui
X
Jiang
Yun-Jin
YJ
D000483:Alleles; D000818:Animals; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009154:Mutation / Q000235:genetics; D016376:Oligonucleotides, Antisense; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C518719:Mib2 protein, zebrafish; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish