| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| In this paper we report that Dorfin , a RING finger type E 3 ubiquitin ligase , is predominantly localized in the inclusion bodies of familial ALS with a copper / zinc superoxide dismutase ( SOD 1 ) mutation as well as sporadic ALS . ^^^ Dorfin physically bound and ubiquitylated various SOD 1 mutants derived from familial ALS patients and enhanced their degradation , but it had no effect on the stability of the wild type SOD 1 . ^^^ Dorfin ubiquitylates mutant SOD 1 and prevents mutant SOD 1 mediated neurotoxicity . ^^^ The overexpression of Dorfin protected against the toxic effects of mutant SOD 1 on neural cells and reduced SOD 1 inclusions . ^^^ Our results indicate that Dorfin protects neurons by recognizing and then ubiquitylating mutant SOD 1 proteins followed by targeting them for proteasomal degradation . . ^^^ |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| Here , we report that affinity purified anti Dorfin antibody labeled ubiquitylated inclusions of Parkinson ' s disease , dementia with Lewy bodies disease , multiple system atrophy , and sporadic and familial ALS . ^^^ These results suggest that Dorfin plays a crucial role in the formation of ubiquitylated inclusions of alpha synucleinopathy and ALS . ^^^ However , because we failed to show the direct binding of alpha synuclein with Dorfin , future investigations into the binding partner ( s ) of Dorfin will be needed to deepen our understanding of the pathophysiology of alpha synucleinopathy and ALS . . ^^^ |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| Abstract Dorfin is a RING finger type ubiquitin ligase for mutant superoxide dismutase 1 ( SOD 1 ) that enhances its degradation . ^^^ In the present study , therefore , we investigated whether Dorfin can modulate the level of mutant SOD 1 in the mitochondria and subsequent caspase activation . ^^^ We showed that Dorfin significantly reduced the amount of mutant SOD 1 in the mitochondria , the release of cytochrome c and the activation of the following caspase cascade , thereby preventing eventual neuronal cell death in a neuronal cell model of FALS . ^^^ These results suggest that reducing the accumulation of mutant SOD 1 in the mitochondria may be a new therapeutic strategy for mutant SOD 1 associated FALS , and that Dorfin may play a significant role in this . . ^^^ Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis . ^^^ |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| Dorfin , a RING IBR type ubiquitin ligase ( E 3 ) , can ubiquitylate mutant superoxide dismutase 1 , the causative gene of familial amyotrophic lateral sclerosis ( ALS ) . ^^^ Dorfin is located in ubiquitylated inclusions ( UBIs ) in various neurodegenerative disorders , such as ALS and Parkinson ' s disease ( PD ) . ^^^ Our results indicate that VCPs functionally regulate Dorfin through direct interaction and that their functional interplay may be related to the process of UBI formation in neurodegenerative disorders , such as ALS or PD . . ^^^ VCP ( K524A ) , a dominant negative form of VCP , reduced the E 3 activity of Dorfin against mutant superoxide dismutase 1 , whereas it had no effect on the autoubiquitylation of Parkin . ^^^ |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis revealed a 40 60 % decrease in ERK 1 , 2 and p 38 protein levels , small modification of phosphorylated Akt expression , and a 30 % increase in SOD 1 protein expression in HG cells . ^^^ |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NV58 and P00441 |
Pubmed |
SVM Score :0.0 |
| NA |
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