Phosphorylation of kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development

Takeshi Terabayashi, Masaji Sakaguchi, Kaori Shinmyozu, Toshio Ohshima, Ai Johjima, Teru Ogura, Hiroaki Miki, Ryuichi Nishinakamura

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    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.

    Original languageEnglish
    Article numbere39714
    JournalPLoS One
    Volume7
    Issue number6
    DOIs
    Publication statusPublished - 2012 Jun 29

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    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Terabayashi, T., Sakaguchi, M., Shinmyozu, K., Ohshima, T., Johjima, A., Ogura, T., Miki, H., & Nishinakamura, R. (2012). Phosphorylation of kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development. PLoS One, 7(6), [e39714]. https://doi.org/10.1371/journal.pone.0039714