NUB1 Suppresses the Formation of Lewy Body-Like Inclusions by Proteasomal Degradation of Synphilin-1

Tanji, Kunikazu; Tanaka, Tomoaki; Mori, Fumiaki; Kito, Katsumi; Takahashi, Hitoshi; Wakabayashi, Keiji; Kamitani, Tetsu

doi:10.2353/ajpath.2006.051067

Cited by 57 publications

(60 citation statements)

References 42 publications

(61 reference statements)

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“…8, C and D), thereby improving UPS function. Supporting the role of NUB1L in proteasome proteolysis, NUB1L promotes the polyubiquitination and clearance of mutant Huntingtin, tau, and synphilin 1 and reduces the formation of inclusions (21)(22)(23). In addition, NUB1L knockdown accumulates Cyclin E and p27, both proteins known to be degraded by the proteasome (42).…”

Section: Discussionmentioning

confidence: 99%

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NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins

et al. 2015

Journal of Biological Chemistry

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Background: NEDD8 conjugates are increased in cells with proteasome function impairment, and neddylation of ubiquitinated proteins on the ubiquitin chain requires ubiquitin-but not NEDD8-activating enzyme. Results: NEDD8 ultimate buster 1 long (NUB1L) suppresses atypical neddylation and promotes the degradation of misfolded proteins. Conclusion: NUB1L is an important regulator of protein quality control. Significance: Selective targeting of atypical neddylation is a novel strategy to enhance protein quality control.

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Section: Discussionmentioning

confidence: 99%

“…NUB1L overexpression has been shown previously to reduce neddylated proteins in non-cardiac cells (19). Moreover, NUB1L controls the degradation of synphilin 1, tau, and mutant Hungtingtin (21)(22)(23), suggesting that NUB1L may play a role in certain neurodegenerative diseases.…”

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confidence: 99%

NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins

et al. 2015

Journal of Biological Chemistry

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“…In addition, inclusion bodies containing a-syn, referred to as Lewy bodies, are pathological hallmarks of familial and sporadic PD (Fujiwara et al, 2002;Tanji et al, 2006). Importantly, a-syn is predominantly phosphorylated at Ser129 (S129) in Lewy bodies of the PD brain (Fujiwara et al, 2002;Anderson et al, 2006).…”

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confidence: 99%

Role of Ser129 phosphorylation of α-synuclein in melanoma cells

Lee

Matsuo

Cashikar

et al. 2013

Journal of Cell Science

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Summary a-Synuclein, a protein central to Parkinson's disease, is frequently expressed in melanoma tissues, but not in non-melanocytic cutaneous carcinoma and normal skin. Thus, a-synuclein is not only related to Parkinson's disease, but also to melanoma. Recently, epidemiologists reported co-occurrence of melanoma and Parkinson's disease in patients, suggesting that these diseases could share common pathogenetic components and that a-synuclein might be one of these. In Parkinson's disease, phosphorylation of a-synuclein at Ser129 plays an important role in the pathobiology. However, its role in melanoma is not known. Here, we show the biological relevance of Ser129 phosphorylation in human melanoma cells. First, we have identified an antibody that reacts with Ser129-unphosphorylated asynuclein but not with Ser129-phosphorylated a-synuclein. Using this and other antibodies to a-synuclein, we investigated the role of Ser129 phosphorylation in human melanoma SK-MEL28 and SK-MEL5 cells. Our immunofluorescence microscopy showed that the Ser129-phosphorylated form, but not the Ser129-unphosphorylated form, of a-synuclein localizes to dot-like structures at the cell surface and the extracellular space. Furthermore, immuno-electron microscopy showed that the melanoma cells release microvesicles in which Ser129-phosphorylated a-synuclein localizes to the vesicular membrane. Taken together, our studies suggest that the phosphorylation of Ser129 leads to the cell surface translocation of a-synuclein along the microtubule network and its subsequent vesicular release in melanoma cells.

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“…Kito et al have also shown that the expression of NUB1 is induced by IFN-b in certain cell lines and that exogenous overexpression of NUB1 inhibits proliferation of U2OS cells, which are deficient in endogenous NUB1 expression . Recently, NUB1 has been reported to inhibit the formation of inclusions such as the Lewy bodies seen in brains of patients with Parkinson's disease (Tanji et al, 2006). As the expression of NEDD8 is downregulated by NUB1, the expression level of NUB1 may control many important biological events, including cell-cycle progression.…”

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confidence: 99%

369 Nub1, an Interferon-Inducible Protein, Mediates Anti-Proliferative Actions and Apoptosis in Renal Cell Carcinoma Cells Through Cell Cycle Regulation

Tanaka¹,

Hosono²,

Kuratsukuri³

et al. 2010

Journal of Urology

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BACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-a was measured by watersoluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-a in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-a correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-a-resistant A498 cells, in which NUB1 is not induced by IFN-a. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-a-resistant A498 cells and suppressed IFN-a-induced growth inhibition in IFN-a-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-a in RCC cells but also in the anti-cancer effect against IFN-a-resistant RCC cells.

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NUB1 Suppresses the Formation of Lewy Body-Like Inclusions by Proteasomal Degradation of Synphilin-1

Cited by 57 publications

References 42 publications

NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins

NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins

Role of Ser129 phosphorylation of α-synuclein in melanoma cells

369 Nub1, an Interferon-Inducible Protein, Mediates Anti-Proliferative Actions and Apoptosis in Renal Cell Carcinoma Cells Through Cell Cycle Regulation

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