title: Phosphorylation of Kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development.
abstract: Kif26b, a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. Kif26b expression is restricted to the metanephric mesenchyme, and its transcription is regulated by a zinc finger transcriptional regulator Sall1. However, the mechanism(s) by which Kif26b protein is regulated remain unknown. Here, we demonstrate phosphorylation and subsequent polyubiquitination of Kif26b in the developing kidney. We find that Kif26b interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney. Phosphorylation of Kif26b at Thr-1859 and Ser-1962 by the cyclin-dependent kinases (CDKs) enhances the interaction of Kif26b with Nedd4. Nedd4 polyubiquitinates Kif26b and thereby promotes degradation of Kif26b via the ubiquitin-proteasome pathway. Furthermore, Kif26b lacks ATPase activity but does associate with microtubules. Nocodazole treatment not only disrupts the localization of Kif26b to microtubules but also promotes phosphorylation and polyubiquitination of Kif26b. These results suggest that the function of Kif26b is microtubule-based and that Kif26b degradation in the metanephric mesenchyme via the ubiquitin-proteasome pathway may be important for proper kidney development.
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Takeshi
authors: T
authors: Terabayashi
authors: Masaji
authors: M
authors: Sakaguchi
authors: Kaori
authors: K
authors: Shinmyozu
authors: Toshio
authors: T
authors: Ohshima
authors: Ai
authors: A
authors: Johjima
authors: Teru
authors: T
authors: Ogura
authors: Hiroaki
authors: H
authors: Miki
authors: Ryuichi
authors: R
authors: Nishinakamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000378:metabolism*; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D000075702:Nedd4 Ubiquitin Protein Ligases; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C487946:KIF26B protein, mouse; D010769:Phosphothreonine; D025821:Polyubiquitin; D010768:Phosphoserine; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases; D046988:Proteasome Endopeptidase Complex; C583839:KIF26B protein, human; D016547:Kinesins