Armadillo Repeat Containing 8α Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins



Koji Tomaru1, Atsuhisa Ueda*, 1, Takeyuki Suzuki1, Nobuaki Kobayashi1, Jun Yang1, Masaki Yamamoto1, Mitsuhiro Takeno1, Takeshi Kaneko2, Yoshiaki Ishigatsubo1
1 Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
2 Department of Pulmonary Medicine, Yokohama City University Medical Center, Yokohama 232-0024, Japan


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© Tomaru et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Internal Medicine and Clinical Immunology Yokohama City University Graduate School of Medicine3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; Tel: +81-45-787-2630; Fax: +81-45-786-3444; E-mail: aueda@med.yokohama-cu.ac.jp


Abstract

Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) α. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8α co-localized with HRS. ARMc8α promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8α.

Keywords: ARMc8α, FBPase, monoubiquitination, HRS, UIM.