Parkin interacts with the proteasome subunit α4

Dächsel, Justus C.; Lücking, Christoph B.; Deeg, Sebastian; Schultz, E.; Łałowski, Maciej; Casademunt, Elisabeth; Corti, Olga; Hampe, Christiane S.; Patenge, Nadja; Vaupel, Kristina; Yamamoto, Ayako; Dichgans, Martin; Brice, Alexis; Wanker, Erich E.; Kahle, Philipp J.; Gasser, Thomas

doi:10.1016/j.febslet.2005.06.003

Cited by 48 publications

(30 citation statements)

References 20 publications

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“…There have been several reports on cellular regulatory proteins and viral proteins that interact with subunits of the proteasome complex and participate in proteasomedependent regulation (42,43). PSMA7 is a subunit of proteasome that regulates the activity of this complex associated with HBX, suggesting that HBX may modulate the function of proteasome by interacting with PSMA7.…”

Section: Discussionmentioning

confidence: 99%

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Wei¹,

Song

et al. 2010

The Journal of Immunology

207

185

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Section: Discussionmentioning

confidence: 99%

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Wei¹,

Song

et al. 2010

The Journal of Immunology

207

185

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“…The gene products targeted in familial PD are either degraded via the UPS (␣-synuclein, parkin, synphilin-1, mutated DJ-1) or integral components of the degradation pathway (parkin, ubiquitin C-terminal hydrolase L1) (Krüger et al, 2002). Parkin has been reported to interact with proteasomal subunits such as Rpn10 (Sakata et al, 2003), Rpt6 (Tsai et al, 2003), and ␣ 4 (Dächsel et al, 2005). In addition, parkin overexpression was found to enhance the proteasomal activity (Hyun et al, 2002;Dächsel et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Parkin Directly Modulates 26S Proteasome Activity

Um¹,

Im²,

Lee³

et al. 2010

J. Neurosci.

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Parkinson's disease (PD) is a common neurodegenerative disease that involves the deterioration of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD remains poorly understood, recent genetic, postmortem, and experimental evidence shows that abnormal protein accumulation and subsequent aggregate formation are prominent features of both sporadic and familial PD. While proteasome dysfunction is observed in PD, diverse mutations in the parkin gene are linked to early-onset autosomalrecessive forms of familial PD. We demonstrate that parkin, an E3 ubiquitin ligase, activates the 26S proteasome in an E3 ligase activityindependent manner. Furthermore, an N-terminal ubiquitin-like domain within parkin is critical for the activation of the 26S proteasome through enhancing the interaction between 19S proteasomal subunits, whereas the PD-linked R42P mutant abolishes this action. The current findings point to a novel role for parkin for 26S proteasome assembly and suggest that parkin mutations contribute to the proteasomal dysfunction in PD.

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“…Recently, Parkin has also been shown to interact with the ␣4 subunit of the 19 S proteasome, although the latter does not appear to serve as a substrate for parkin-directed ubiquitination (10). Substantial accumulations of Parkin are found associated with ␣-synuclein and ubiquitin bearing Lewy bodies in Parkinson disease and dementia with Lewy bodies (11), suggesting a role in the pathologic sequestration of proteins in these disorders.…”

mentioning

confidence: 99%

Parkin Protects against Mitochondrial Toxins and β-Amyloid Accumulation in Skeletal Muscle Cells

Rosen

Veereshwarayya

Moussa

et al. 2006

Journal of Biological Chemistry

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Mutations in the ubiquitin ligase-encoding Parkin gene have been implicated in the pathogenesis of autosomal recessive Parkinson disease. Outside of the central nervous system, Parkin is prominently expressed in skeletal muscle. We have found accumulations of Parkin protein in skeletal muscle biopsies taken from patients with inclusion body myositis, a degenerative disorder in which intramyofiber accumulations of the ␤-amyloid peptide are pathognomonic. In comparing primary cultures of skeletal muscle derived from parkin knock-out and wild-type mice, we have found the absence of parkin to result in greater sensitivity to mitochondrial stressors rotenone and carbonyl cyanide 3-chlorophenylhydrazone, without any alteration in sensitivity to calcium ionophore or hydrogen peroxide. Utilizing viral expression constructs coding for the Alzheimer disease and inclusion body myositis-linked ␤-amyloid precursor protein and for its metabolic byproducts A␤42 and C100, we found that parkin knock-out muscle cells are also more sensitive to the toxic effects of intracellular A␤. We also constructed a lentiviral system to overexpress wild-type Parkin and have shown that boosting the levels of parkin expression in normal skeletal muscle cultures provides substantial protection against both mitochondrial toxins and overexpressed ␤-amyloid. Correspondingly, exogenous Parkin significantly lowered A␤ levels. These data support the hypothesis that in myocytes parkin has dual properties in the maintenance of skeletal muscle mitochondrial homeostasis and in the regulation of A␤ levels. The Parkin protein is considered an E33 ubiquitin ligase and when mutated has been linked to the development of autosomal recessive Parkinson disease (1-3). In overexpression (or in cellular) models it functions to modify specific target proteins by ubiquitination, earmarking them for proteasomal degradation (3). Putative targets of Parkin include, among others, Pael-R (Parkin-associated endothelin-like receptor) (4), synphilin-1 (5), a modified form of ␣-synuclein (6), CDCrel1 (7), and p38/JTV-1, an aminoacyl-tRNA synthetase cofactor (8). Previous reports have indicated that the cellular stress response promotes the formation of a complex between Parkin, the chaperone Hsp70, the C terminus of Hsc70 interacting protein CHIP, and Pael-R (9). Recently, Parkin has also been shown to interact with the ␣4 subunit of the 19 S proteasome, although the latter does not appear to serve as a substrate for parkin-directed ubiquitination (10). Substantial accumulations of Parkin are found associated with ␣-synuclein and ubiquitin bearing Lewy bodies in Parkinson disease and dementia with Lewy bodies (11), suggesting a role in the pathologic sequestration of proteins in these disorders. Although parkin mRNA is expressed throughout the central nervous system, it is also prominently expressed in skeletal and cardiac muscle, tissues with sustained levels of protein turnover (1).Although Parkin can be found in both cytosolic and membrane-associated compartments of the cel...

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Parkin interacts with the proteasome subunit α4

Cited by 48 publications

References 20 publications

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Parkin Directly Modulates 26S Proteasome Activity

Parkin Protects against Mitochondrial Toxins and β-Amyloid Accumulation in Skeletal Muscle Cells

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