FBXO7 Y52C Polymorphism as a Potential Protective Factor in Parkinson's Disease
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{"title"=>"FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease", "type"=>"journal", "authors"=>[{"first_name"=>"Chiung Mei", "last_name"=>"Chen", "scopus_author_id"=>"7501947651"}, {"first_name"=>"I. G.", "last_name"=>"Chen", "scopus_author_id"=>"56271579400"}, {"first_name"=>"Yi Cheng", "last_name"=>"Huang", "scopus_author_id"=>"35214939800"}, {"first_name"=>"Hsueh Fen", "last_name"=>"Juan", "scopus_author_id"=>"7007126387"}, {"first_name"=>"Ying Lin", "last_name"=>"Chen", "scopus_author_id"=>"56273216300"}, {"first_name"=>"Yi Chun", "last_name"=>"Chen", "scopus_author_id"=>"57133240000"}, {"first_name"=>"Chih Hsin", "last_name"=>"Lin", "scopus_author_id"=>"25639005500"}, {"first_name"=>"Li Ching", "last_name"=>"Lee", "scopus_author_id"=>"7404389959"}, {"first_name"=>"Chi Mei", "last_name"=>"Lee", "scopus_author_id"=>"57139701700"}, {"first_name"=>"Guey Jen", "last_name"=>"Lee-Chen", "scopus_author_id"=>"7003879073"}, {"first_name"=>"Yun Ju", "last_name"=>"Lai", "scopus_author_id"=>"8529305600"}, {"first_name"=>"Yih Ru", "last_name"=>"Wu", "scopus_author_id"=>"7406894171"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0101392", "sgr"=>"84904359872", "issn"=>"19326203", "pui"=>"373542230", "pmid"=>"25029497", "scopus"=>"2-s2.0-84904359872"}, "id"=>"d84bc6c1-74fb-3799-bba8-cd9e9a8c1ceb", "abstract"=>"<p>Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ?50) and only two known variants, Y52C (c.155A&gt;G) and M115I (c.345G&gt;A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese. � 2014 Chen et al.</p>", "link"=>"http://www.mendeley.com/research/fbxo7-y52c-polymorphism-potential-protective-factor-parkinsons-disease", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1596982"], "description"=>"<p>Odds ratios were calculated by comparing each value with the major common genotype or allele.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "allele", "distributions"], "article_id"=>1107584, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.t002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genotype_and_allele_distributions_and_association_analysis_/1107584", "title"=>"Genotype and allele distributions and association analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596971"], "description"=>"<p>HEK-293T cells were tranfected with Tyr52 or Cys52 FBXO7 construct and harvested after two days. Transfected FBXO7-EGFP or endogenous TRAF2 protein was detected using specific antibodies and anti-actin and anti-neomycin antibodies as the loading and the transfection control, respectively. Data are represented as the means ± S.D. of three separate experiments.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "blot", "pathway"], "article_id"=>1107573, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_of_NF_954_B_signaling_pathway_protein_TRAF2_/1107573", "title"=>"Western blot analysis of NF-κB signaling pathway protein TRAF2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596967"], "description"=>"<p>(A) Confocal microscopy examination of Tyr52 and Cys52 FBXO7-EGFP protein in HEK-293T cells. HEK-293T cells were transfected with Tyr52 and Cys52 FBXO7-EGFP for two days and stained with DAPI to detect nuclei. The green (FBXO7 fusion protein) to blue (nuclei staining) fluorescence signal was quantified and shown below. (B) Western blot analysis of pEGFP-N1 vector (Vec) and Tyr52 (WT) and Cys52 FBXO7-EGFP transfected cells using FBXO7 antibody and anti-tubulin and anti-neomycin antibodies as loading and transfection controls, respectively. (C) Tyr52 and Cys52 FBXO7-EGFP proteins in transfected cells were analyzed after blocking of new protein synthesis in a cycloheximide (200 µg/ml) chase experiment (cells were harvested after 6, 12, 24, 36, and 48 hr). Data are represented as the means ± S.D. of three separate experiments.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "fbxo7", "hek-293t"], "article_id"=>1107569, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_FBXO7_protein_in_HEK_293T_cells_/1107569", "title"=>"Expression of FBXO7 protein in HEK-293T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596965"], "description"=>"<p>(A) Chromatograms of direct cDNA sequencing of Y52C and M115I. (B) Restriction analysis of Y52C and M115I. On agarose gel, Y52C creates new <i>Pst</i>I restriction site by mismatch PCR and leads to an additional 222 bp band, whereas M115I loses restriction by <i>Pae</i>I and leads to 479 bp band. (C) Evolutionary conservation of the regions of FBXO7 Y52C and M115I using the program Vector NTI.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "amino"], "article_id"=>1107567, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variant_identification_and_amino_acid_sequence_alignment_/1107567", "title"=>"Variant identification and amino acid sequence alignment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596973"], "description"=>"<p>(A) HEK-293T cells were transiently transfected with Tyr52 or Cys52 FBXO7-EGFP construct. After 48 h, cell lysates were prepared (Input, left panel) and immunoprecipitations (IP, right panel) were performed with anti-TRAF2 antibody. Normal IgG was used as a negative control for IP. Cell lysates and immunoprecipitates were analyzed with anti-EGFP, anti-TRAF2, anti-ubiquitin or anti-actin antibody. (B) Quantification of immunoprecipitated FBXO7-EGFP, TRAF2 and ubiquitin in HEK-293T cells transiently transfected with Tyr52 or Cys52 FBXO7-EGFP construct for 2 days. Data are represented as the means ± S.D. of three separate experiments.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "tyr52", "cys52", "fbxo7-egfp", "ubiquitination"], "article_id"=>1107575, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g005", "stats"=>{"downloads"=>0, "page_views"=>63, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_immunoprecipitation_of_Tyr52_or_Cys52_FBXO7_EGFP_protein_and_ubiquitination_of_TRAF2_/1107575", "title"=>"Co-immunoprecipitation of Tyr52 or Cys52 FBXO7-EGFP protein and ubiquitination of TRAF2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596974"], "description"=>"<p>(A) HEK-293T and SH-SY5Y cells were transfected with FBXO7-specific or control siRNA. After 48 h, cell lysates were prepared and Western blot analysis was performed using FBXO7 and anti-actin (as loading control) antibodies. (B) HEK-293T and SH-SY5Y cells were transfected with siRNA (FBXO7-specific or control), FBXO7 cDNA or not (−). After 24 hr, cells were treated with MPP<sup>+</sup> (300 µM for HEK-293T or 2 mM for SH-SY5Y) and toxic effects of MPP<sup>+</sup> were monitored at 24 hr by MTT assay.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "fbxo7", "suppressed", "over-expressed"], "article_id"=>1107576, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g006", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Toxic_effects_of_MPP_in_FBXO7_suppressed_or_over_expressed_cells_/1107576", "title"=>"Toxic effects of MPP<sup>+</sup> in FBXO7 suppressed or over-expressed cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596969"], "description"=>"<p>Protein models were shown in secondary representation. Tyr52 and Cys52 residue were shown in amino acid structures. The hydrogen bond interaction was presented in yellow dash line.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "homology", "tyr52", "fbxo7", "cys52"], "article_id"=>1107571, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_homology_models_of_Tyr52_WT_FBXO7_and_Cys52_Y52C_/1107571", "title"=>"The homology models of Tyr52 (WT) FBXO7 and Cys52 (Y52C).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596983"], "description"=>"<p>The <i>Pst</i>I restriction site was created by PCR using a mismatch primer. For Y52C and M115I amplification, the underlines in the primer sequence and enzyme recognition site indicate the mismatch nucleotide and polymorphic site, respectively. For cDNA cloning, the underlines in the primer sequence indicate the introduced <i>Hin</i>dIII, <i>Age</i>I and <i>Xho</i>I restriction sites.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "pcr", "amplification", "cdna", "genomic"], "article_id"=>1107585, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.t001", "stats"=>{"downloads"=>3, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primers_and_conditions_for_PCR_amplification_of_FBXO7_cDNA_and_genomic_DNA_/1107585", "title"=>"Primers and conditions for PCR amplification of <i>FBXO7</i> cDNA and genomic DNA.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-16 03:18:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1596981"], "description"=>"<p>(A) Western blot analysis of FBXO7-EGFP protein level using FBXO7 antibody and anti-actin antibody as loading control after 2 days induction with doxycycline (+ Dox) or not (- Dox). (B) Representative microscopic images of neuronal differentiated Tyr52 and Cys52 cells (for 21 days). Nuclei were counterstained with DAPI (blue). Neuronal total outgrowth was quantified in Tyr52 and Cys52 cells with induced differentiation for 7–21 days. Data are represented as the means ± S.D. of three separate experiments.</p>", "links"=>[], "tags"=>["genetics", "Gene function", "Genetics of disease", "neuroscience", "neurology", "Neurodegenerative diseases", "Movement disorders", "Parkinson disease", "Neurobiology of disease and regeneration", "sh-sy5y", "cells", "induced", "fbxo7", "neuronal"], "article_id"=>1107583, "categories"=>["Biological Sciences"], "users"=>["Chiung-Mei Chen", "I-Cheng Chen", "Yi-Cheng Huang", "Hsueh-Fen Juan", "Ying-Lin Chen", "Yi-Chun Chen", "Chih-Hsin Lin", "Li-Ching Lee", "Chi-Mei Lee", "Guey-Jen Lee-Chen", "Yun-Ju Lai", "Yih-Ru Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0101392.g007", "stats"=>{"downloads"=>1, "page_views"=>132, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flp_In_SH_SY5Y_cells_with_induced_FBXO7_expression_and_neuronal_phenotype_/1107583", "title"=>"Flp-In SH-SY5Y cells with induced FBXO7 expression and neuronal phenotype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-16 03:18:20"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}]}
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