title: Characterization of a brain-enriched chaperone, MRJ, that inhibits Huntingtin aggregation and toxicity independently.
abstract: Molecular chaperones are involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. DnaK- and DnaJ-like proteins are the two major classes of molecular chaperones in mammals. Recent studies have shown that DnaJ-like family proteins can inhibit polyglutamine aggregation, a hallmark of many neurodegenerative diseases, including Huntington's disease (HD). Although most DnaJ-like proteins studied are ubiquitously expressed, some have restricted expression, so it is possible that some specific chaperones may affect polyglutamine aggregation in specific neurons. In this report, we describe the isolation of a DnaJ-like protein MRJ and the characterization of its chaperone activity. Tissue distribution studies showed that MRJ is highly enriched in the central nervous system. In an in vitro cell model of HD, overexpressed MRJ effectively suppressed polyglutamine-dependent protein aggregation, caspase activity, and cellular toxicity. Collectively, these results suggest that MRJ has a relevant functional role in neurons.
authors.affiliation: Department of Ophthalmology, Weill Medical College of Cornell University, New York, New York 10012, USA.
authors.forename: Jen-Zen
authors.initials: JZ
authors.lastname: Chuang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Meicai
authors.initials: M
authors.lastname: Zhu
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Sung
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002470:Cell Survival; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D007150:Immunohistochemistry; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000737:chemistry*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; C485565:DNAJB6 protein, human; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine; D000251:Adenosine Triphosphatases; C063842:dnaK protein, E coli