title: Protective role of the ubiquitin binding protein Tollip against the toxicity of polyglutamine-expansion proteins.
abstract: Huntington disease (HD) is caused by the expansion of polyglutamine (polyQ) repeats in the amino-terminal of hungtintin (htt). PolyQ-expanded htt forms intracellular ubiquitinated aggregates in neurons and causes neuronal cell death. Here, utilizing a HD cellular model, we report that Tollip, an ubiquitin binding protein that participates in intracellular transport via endosomes, co-localizes with and stimulates aggregation of polyQ-expanded amino-terminal htt. Furthermore, we demonstrate that Tollip protects cells against the toxicity of polyQ-expanded htt. We propose that association of Tollip with polyubiquitin accelerates aggregation of toxic htt species into inclusions and thus provides a cell protective role by sequestration.
authors: Department of Life Sciences, The Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors: Asami
authors: A
authors: Oguro
authors: Hiroshi
authors: H
authors: Kubota
authors: Miho
authors: M
authors: Shimizu
authors: Shoichi
authors: S
authors: Ishiura
authors: Yoriko
authors: Y
authors: Atomi
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D057809:HEK293 Cells; D006801:Humans; D000071058:Huntingtin Protein; D007150:Immunohistochemistry; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D034622:RNA Interference; D015842:Serine Proteinase Inhibitors; D025801:Ubiquitin / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D010455:Peptides; D050765:Qa-SNARE Proteins; D015842:Serine Proteinase Inhibitors; C410602:TOLLIP protein, human; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D049452:Green Fluorescent Proteins; C097188:polyglutamine; C007293:DAPI