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A cellular system that degrades misfolded proteins and protects against neurodegeneration


, : A cellular system that degrades misfolded proteins and protects against neurodegeneration. Molecular Cell 55(1): 15-30

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 nucleus. PML selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. SUMOylated misfolded proteins are then recognized and ubiquitinated by RNF4 and are subsequently targeted for proteasomal degradation. We further show that PML deficiency exacerbates polyglutamine (polyQ) disease in a mouse model of spinocerebellar ataxia 1 (SCA1). These findings reveal a mammalian system that removes misfolded proteins through sequential SUMOylation and ubiquitination and define its role in protection against protein-misfolding diseases.

US$19.90

PMID: 24882209

DOI: 10.1016/j.molcel.2014.04.030


Other references

Bohli-Abderrazak, D.; Ayari, A.; Morgan, E.; Nasri-Ammar, K., 2012: Towards a characterization of the locomotor activity rhythm of the supralittoral isopod Tylos europaeus. Freshly collected samples of Tylos europaeus from Korba beach (northeast of Tunisia) were housed in an environmental cabinet at controlled temperature (18°C ± .5°C) and photoperiod. Locomotor activity was recorded under two photoperiodic re...

Lohr, D.E., 1981: Detailed analysis of the nucleosomal organization of transcribed DNA in yeast chromatin. The precise chromatin structure of actively transcribed DNA in yeast has been analyzed by electrophoretic transfer of high-resolution staphylococcal nuclease and DNase I chromatin digest DNA patterns to DBM paper and hybridization with active sequ...

Beyer, K.H.; Bothe, W., 1973: The quantitative determination of diquat in biological material. Permutit R S 40, an acid ion exchange resin, can be used to determine the herbicide diquat. This compound is eluted by the ion exchange column with a cold saturated NH4Cl solution. The spectrophotometric determination is carried through after redu...

Wujak, Łukasz.A.; Blume, A.; Baloğlu, E.; Wygrecka, Młgorzata.; Wygowski, J.; Herold, S.; Mayer, K.; Vadász, Ián.; Besuch, P.; Mairbäurl, H.; Seeger, W.; Morty, R.E., 2016: FXYD1 negatively regulates Na(+)/K(+)-ATPase activity in lung alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is clinical syndrome characterized by decreased lung fluid reabsorption, causing alveolar edema. Defective alveolar ion transport undertaken in part by the Na(+)/K(+)-ATPase underlies this compromised flu...

Davis, K.R.; Darvill, A.G.; Albersheim, P., 1986: Several biotic and abiotic elicitors act synergistically in the induction of phytoalexin accumulation in soybean. Plants often respond to microbial infection by producing antimicrobial compounds called phytoalexins. Plants also produce phytoalexins in response to in vitro treatment with molecules called elicitors. Specific elicitors, including a hexa-β-gluco...

Murao, M.; Terai, T.; Kirisawa, T.; Kon, H.; Moriyama, Y.; Hattori, T., 1981: Clinical experience of therapeutic use of cefmetazole (cefmetazon) or bronchopneumonia. 1. Therapeutic effects of cefmetazole (cefmetazon, CMZ) were examined in 22 cases of bronchopneumonia. 2. Among the 22 cases, 17 cases (77%) showed better response than 'effective'. However, 10 cases (91%) showed better response than &ap...

Playter, R.F.; Ellett, E.W., 1972: Ectopic cilia (a case report). Veterinary Medicine, Small Animal Clinician 67(5): 532-533

Wardle, J.; Watters, R., 2004: Sociocultural influences on attitudes to weight and eating: results of a natural experiment. Objective: Exposure to teenage culture is widely believed to contribute to concerns about weight in children and adolescents. The current study tested the hypothesis that greater exposure to older girls at school would be associated with thinner s...

Keller, C.; Lang, K., 1956: Effect of the cyclophorase system on valine, tryptophan and histidine. Biochemische Zeitschrift 328(4): 285-290

Steindel, S.J., 2012: A comparison between a SNOMED CT problem list and the ICD-10-CM/PCS HIPAA code sets. In 2013 the United States will convert from the use of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the use of the International Classification of Diseases, Tenth Revision, Clinical Modification...