A Cellular System that Degrades Misfolded Proteins and Protects against Neurodegeneration

• Published in: Molecular cell Vol. 55; no. 1; pp. 15 - 30
• Main Authors: Guo, Lili, Giasson, Benoit I., Glavis-Bloom, Alex, Brewer, Michael D., Shorter, James, Gitler, Aaron D., Yang, Xiaolu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.07.2014
• Subjects: animal models; Animals; ataxia (disorder); Ataxin-1; Ataxins; cell nucleus; Humans; mammals; Mice; Models, Biological; Nerve Degeneration - pathology; Nerve Tissue Proteins - metabolism; neurodegenerative diseases; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Promyelocytic Leukemia Protein; Proteasome Endopeptidase Complex; Protein Folding; proteins; Proteolysis; Spinocerebellar Ataxias - genetics; Spinocerebellar Ataxias - metabolism; Sumoylation; Transcription Factors - metabolism; Transcription Factors - physiology; Tumor Suppressor Proteins - metabolism; Tumor Suppressor Proteins - physiology; Ubiquitin; ubiquitin-protein ligase; Ubiquitination

Misfolded proteins compromise cellular function and cause disease. How these proteins are detected and degraded is not well understood. Here we show that PML/TRIM19 and the SUMO-dependent ubiquitin ligase RNF4 act together to promote the degradation of misfolded proteins in the mammalian cell nucleu...