Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood

Kasap, Murat; Akpınar, Gürler; Sazcı, Ali; İdrisoğlu, Halil Atilla; Vahaboğlu, Haluk

doi:10.1016/j.neulet.2009.05.079

Cited by 20 publications

(17 citation statements)

References 23 publications

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“…In the present paper, we have described, for the first time, parkin isoforms expression both in total and LMN subpopulations such as T lymphocyte (CD2+), monocyte (CD14+) and B lymphocyte (CD19+). To date, few papers have studied parkin expression in human blood [26,27]. Previously, Sunada et al [26] have identified parkin splice variants in healthy human peripheral leucocytes, even if they underlined that the full-length transcript was hardly detectable in this cellular population.…”

Section: Discussionmentioning

confidence: 99%

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Expression Profile of Human PARK2 Splicing Isoforms in Peripheral Blood Cells and Isolated Lymphomonocytes

2016

ARC Journal of Neuroscience

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Mutations in Parkin gene are responsible of 50% of cases with autosomal recessive juvenile-onsetParkinson's disease (ARJP). Although 21 parkin alternative splice variants have been cloned so far, most of the studies have focused their attention on the full-length protein. Despite the expression of the originally cloned protein has been observed in human blood cells, there is currently no study that has investigated the expression profile of parkin isoforms in human lymphomonocyte (LMN). In the present study, we have explored the expression pattern of parkin proteins in total LMN and in specific subpopulations like T lymphocyte (CD2+), monocyte (CD14+) and B lymphocyte (CD19+).Peripheral blood was collected from healthy volunteers (n=5). Total LMN homogenate expresses H1, H5 and H6 parkin isoforms. These data have been confirmed by immunoprecipitation analysis, by using three antibodies recognizing different domains of the full-length. In human CD2+, CD14+ and CD19+ subpopulations, two bands of ~58 and ~52 kDa molecular weight have been revealed. These proteins are distributed both in cytoplasm and nucleus, as demonstrated by fluorescence immunolocalization. The expression of parkin isoforms in human blood cells is subpopulation-specific, and is likely altered in PD patients. A future investigation of the parkin splicing profile in human blood cells could represent a useful tool for identify early non-invasive biomarkers in patients affected by ARJP.

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Section: Discussionmentioning

confidence: 99%

“…A shorter and hardly detectable isoform compared to the full length was revealed in these cells. Instead, Kasap et al [27] found a variant of about ~52 kDa molecular weight in the serum of nine patients with Parkinson disease.…”

Section: Introductionmentioning

confidence: 96%

Expression Profile of Human PARK2 Splicing Isoforms in Peripheral Blood Cells and Isolated Lymphomonocytes

2016

ARC Journal of Neuroscience

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“…To date there exists only one paper that has dealt with parkin amino acid sequencing [47]. Trying to ensure that the signal observed on human serum by western blot analysis belongs to parkin protein, they cut off the area on the blot between 50 and 55 kDa in two separate pieces and performed a MALDI-TOF analysis on each.…”

Section: Evidences Of Multiple Parkin Isoforms In Brainmentioning

confidence: 99%

Alternative Splicing Generates Different Parkin Protein Isoforms: Evidences in Human, Rat, and Mouse Brain

Scuderi

Cognata

Drago

et al. 2014

BioMed Research International

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Parkinson protein 2, E3 ubiquitin protein ligase (PARK2) gene mutations are the most frequent causes of autosomal recessive early onset Parkinson's disease and juvenile Parkinson disease. Parkin deficiency has also been linked to other human pathologies, for example, sporadic Parkinson disease, Alzheimer disease, autism, and cancer. PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification. To date several PARK2 splice variants have been identified; however, the expression and distribution of parkin isoforms have not been deeply investigated yet. Here, the currently known PARK2 gene transcripts and relative predicted encoded proteins in human, rat, and mouse are reviewed. By analyzing the literature, we highlight the existing data showing the presence of multiple parkin isoforms in the brain. Their expression emerges from conflicting results regarding the electrophoretic mobility of the protein, but it is also assumed from discrepant observations on the cellular and tissue distribution of parkin. Although the characterization of each predicted isoforms is complex, since they often diverge only for few amino acids, analysis of their expression patterns in the brain might account for the different pathogenetic effects linked to PARK2 gene mutations.

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“…Both western blot and immunofluorescence assays demonstrate not only a quantitative difference in Park2 expression levels between these cell types, but also a different expression pattern of splice isoforms. The expression of PARK2 has been recently assessed in human blood [50]. This study revealed the presence of different splice variants and protein isoforms.…”

Section: Differential Expression Of Park2 In Tissues and Cellsmentioning

confidence: 99%

Increasing the Coding Potential of Genomes Through Alternative Splicing: The Case of PARK2 Gene

Cognata

Iemmolo

D’Agata

et al. 2014

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The completion of the Human Genome Project aroused renewed interest in alternative splicing, an efficient and widespread mechanism that generates multiple protein isoforms from individual genes. Although our knowledge about alternative splicing is growing exponentially, its real impact on cellular life is still to be clarified. Connecting all splicing features (genes, splice transcripts, isoforms, and relative functions) may be useful to resolve this tangle. Herein, we will start from the case of a single gene, Parkinson protein 2, E3 ubiquitin protein ligase (PARK2), one of the largest in our genome. This gene is implicated in the pathogenesis of autosomal recessive juvenile Parkinsonism and it has been recently linked to cancer, leprosy, autism, type 2 diabetes mellitus and Alzheimer’s disease. PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification and protein diversity in tissues and cells. This review will provide an update of all human PARK2 alternative splice transcripts and isoforms presently known, and correlate them to those in rat and mouse, two common animal models for studying human disease genes. Alternative splicing relies upon a complex process that could be easily altered by both cis and trans-acting mutations. Although the contribution of PARK2 splicing in human disease remains to be fully explored, some evidences show disruption of this versatile form of genetic regulation may have pathological consequences.

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Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood

Cited by 20 publications

References 23 publications

Expression Profile of Human PARK2 Splicing Isoforms in Peripheral Blood Cells and Isolated Lymphomonocytes

Expression Profile of Human PARK2 Splicing Isoforms in Peripheral Blood Cells and Isolated Lymphomonocytes

Alternative Splicing Generates Different Parkin Protein Isoforms: Evidences in Human, Rat, and Mouse Brain

Increasing the Coding Potential of Genomes Through Alternative Splicing: The Case of PARK2 Gene

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