title: Mahogunin ring finger-1 (MGRN1) suppresses chaperone-associated misfolded protein aggregation and toxicity.
abstract: Impairment in the elimination of misfolded proteins generates cellular toxicity and leads to various late-onset neurodegenerative diseases. However, the mechanisms by which cells recognize abnormal cellular proteins for selective clearance remain unknown. Lack of the mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase in mice causes the development of age-dependent spongiform neurodegeneration. Here, we report for the first time that the MGRN1 E3 ubiquitin ligase interacts and nicely co-localizes with the cytosolic molecular chaperone Hsp70. The expression of MGRN1 increased following exposure to a variety of stressors. The inhibition of autophagy not only elevated endogenous MGRN1 levels but also caused MGRN1 to be recruited to cytosolic ubiquitin-positive inclusion bodies. Finally, we showed that the overexpression of MGRN1 protects against cell death mediated by oxidative and endoplasmic reticulum stress. These data suggest that MGRN1 selectively targets misfolded proteins for degradation and may exhibit viable therapeutic potential for the treatment of spongiform neurodegeneration.
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India 342011.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chhangani
authors.forename: Amit
authors.initials: A
authors.lastname: Mishra
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017510:Protein Folding; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D045304:Cytochromes c; D008156:Luciferases; C470690:MGRN1 protein, human; D044767:Ubiquitin-Protein Ligases