Mind bomb-2 is an E3 ligase for Notch ligand.
The zebrafish gene, mind bomb (mib), encodes a protein that positively regulates of the Delta-mediated Notch signaling. It interacts with the intracellular domain of Delta to promote its ubiquitination and endocytosis. In our search for the mouse homologue of zebrafish mind bomb, we cloned two homologues in the mouse genome: a mouse orthologue (mouse mib1) and a paralogue, named mind bomb-2 (mib2), which is evolutionarily conserved from Drosophila to human. Both Mib1 and Mib2 have an E3 ubiquitin ligase activity in their C-terminal RING domain and interact with Xenopus Delta (XD) via their N-terminal region. Mib2 is also able to ligate ubiquitin to XD and shift the membrane localization of Delta to intracellular vesicles. Importantly, Mib2 rescues both the neuronal and vascular defects in the zebrafish mib(ta52b) mutants. In contrast to the functional similarities between Mib1 and Mib2, mib2 is highly expressed in adult tissues, but almost not at all in embryos, whereas mib1 is abundantly expressed in both embryos and adult tissues. These data suggest that Mib2 has functional similarities to Mib1, but might have distinct roles in Notch signaling as an E3 ubiquitin ligase.
Koo
Bon-Kyoung
BK
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784 South Korea.
Yoon
Ki-Jun
KJ
Yoo
Kyeong-Won
KW
Lim
Hyoung-Soo
HS
Song
Ran
R
So
Ju-Hoon
JH
Kim
Cheol-Hee
CH
Kong
Young-Yun
YY
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004330:Drosophila; D029721:Drosophila Proteins; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014981:Xenopus; D015027:Zebrafish; D029961:Zebrafish Proteins
D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D012333:RNA, Messenger; D051880:Receptors, Notch; D025801:Ubiquitin; D029961:Zebrafish Proteins; C502454:Mib2 protein, mouse; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish