title: Toll-interacting protein pathway: degradation of an ubiquitin-binding protein.
abstract: The nine neurodegenerative disorders including Huntington disease (HD) are caused by the expansion of a trinucleotide CAG repeats (polyQ), which are located within the coding of the affected gene. Previous studies suggested that a gain of toxic function by polyQ repeats is widely thought to have a major role in pathogenesis. PolyQ-expanded htt induced ubiquitinated aggregates cause cell death in neuronal cells. Using a HD cellular model, we demonstrate that Tollip protects cells against the toxicity of polyQ-expanded htt and also protects cells from death (Oguro, Kubota, Shimizu, Ishiura, & Atomi, 2011). Tom1 which belongs to the VHS domain-containing protein family is also found to be directly binding to ubiquitin chains and Tollip (Katoh et al., 2004; Yamakami, Yoshimori, & Yokosawa, 2003). Tollip recruits misfolded protein to aggresome via late endosome. The cell system can be used to determine if your protein of interest is controlled under a part of Tollip pathway or not among other cell homeostatic systems: molecular chaperons, autophagy, and endoplasmic reticulum (ER)-associated degradation (ERAD). Tollip can be used for polyQ cell toxicity sensor by detecting microtubule-dependent trafficking and aggresome colocalization of aggregated protein.
authors.affiliation: Graduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan; Radioisotope Center, Cell to Body Dynamics Laboratory 1, The University of Tokyo, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Asami
authors.initials: A
authors.lastname: Oguro-Ando
authors.affiliation: Graduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan; Radioisotope Center, Cell to Body Dynamics Laboratory 1, The University of Tokyo, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ohoto-Fujita
authors.affiliation: Graduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan; Radioisotope Center, Cell to Body Dynamics Laboratory 1, The University of Tokyo, Tokyo, Japan. Electronic address: atomi@bio.c.u-tokyo.ac.jp.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Atomi
mesh_terms: D016923:Cell Death; D002460:Cell Line; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C410602:TOLLIP protein, human; D025801:Ubiquitin; D049452:Green Fluorescent Proteins
keywords: Aggregation; Endosome; Huntingtin; Polyglutamine; Tollip