The C-terminus of PARK2 is required for its self-interaction, solubility and role in the spindle assembly checkpoint

Chen, Yvan; Fang, Shang-Ting; Yeh, Pei-Chi; Yang, Hsin-Chia; Chen, Shin-Yuan; Chang, Chih-Jui; Zhai, Wei-Jun; Chen, Yi Cheng; Juang, Yue‐Li

doi:10.1016/j.bbadis.2011.12.007

Cited by 10 publications

(9 citation statements)

References 41 publications

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“…To understand the molecular mechanisms underlying the role of parkin in pancreatic cancer, we analyzed its subcellular localization during the cell cycle. Consistent with previous findings, 25,26 we found that in interephase cells parkin had punctate distribution in the cytosol and prominent accumulation in the perinuclear region (Fig. 4A).…”

Section: Resultssupporting

confidence: 93%

“…26 In addition, parkin has been implicated in the spindle assembly checkpoint, although the molecular details remain to be uncovered. 25 In the present study, our data reveal that in mitosis, parkin is mainly localized at the spindle poles, with modest distribution at the central spindle and the midbody. Consistent with the localization pattern of parkin, silencing of its expression results in a remarkable increase in the percentage of cells with metastasize and therapeutic resistance.…”

Section: Discussionsupporting

confidence: 59%

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Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation

et al. 2013

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Parkin, an E3 ubiquitin ligase well known for its role in the pathogenesis of juvenile Parkinson disease, has been considered as a candidate tumor suppressor in certain types of cancer. It remains unknown whether parkin is involved in the development of pancreatic cancer, the fourth leading cause of cancer-related deaths worldwide. Herein, we demonstrate the downregulation and copy number loss of the parkin gene in human pancreatic cancer specimens. The expression of parkin negatively correlates with clinicopathological parameters indicating the malignancy of pancreatic cancer. In addition, knockdown of parkin expression promotes the proliferation and tumorigenic properties of pancreatic cancer cells both in vitro and in mice. We further find that parkin deficiency increases the proportion of cells with spindle multipolarity and multinucleation. Parkin-depleted cells also show a significant increase in spindle misorientation. These findings indicate crucial involvement of parkin deficiency in the pathogenesis of pancreatic cancer.

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 59%

Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation

et al. 2013

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“…11 A C-terminal truncation of parkin results in a spindle assembly checkpoint defect in the S-to M-phase. 21 Parkin may inhibit the growth of human cervical cancer cells by decreasing the 40S ribosomal protein SA (RPSA) expression and inducing phosphorylation of cytokeratin 8/18. 22 Parkin, as a novel component in the p53 tumor suppression pathway, contributes to the functions of p53 in regulating energy metabolism, especially the Warburg effect, and antioxidant defense.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma

Zhou

Yuan

et al. 2017

Tumour Biol.

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This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.

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“…Besides, the localization of Park2 protein at microtubules is an important factor for its ubiquitin ligase activity toward misfolded substrates. Park5 or UCHL1 gene provides instruction to produce ubiquitin carboxyl-terminal esterase L1 enzyme, and UCHL1 is a member of deubiquitylating enzymes (DUBs) that reverse the action of ubiquitylation reactions in ubiquitin-proteosome pathway (Chen et al 2012;Kahle et al 2009). Park7 mRNA or also known as of DJ-1 gene is a ubiquitous redoxresponsive neuroprotective protein with diverse functions.…”

Section: Discussionmentioning

confidence: 99%

Quercetin Glycosides Induced Neuroprotection by Changes in the Gene Expression in a Cellular Model of Parkinson’s Disease

et al. 2014

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Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease.

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The C-terminus of PARK2 is required for its self-interaction, solubility and role in the spindle assembly checkpoint

Cited by 10 publications

References 41 publications

Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation

Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma

Quercetin Glycosides Induced Neuroprotection by Changes in the Gene Expression in a Cellular Model of Parkinson’s Disease

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