PMID- 25029497
OWN - NLM
STAT- MEDLINE
DCOM- 20150309
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.
PG  - e101392
LID - 10.1371/journal.pone.0101392 [doi]
LID - e101392
AB  - 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>G) and M115I (c.345G>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.
FAU - Chen, Chiung-Mei
AU  - Chen CM
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taipei, Taiwan.
FAU - Chen, I-Cheng
AU  - Chen IC
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taipei, Taiwan.
FAU - Huang, Yi-Cheng
AU  - Huang YC
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Juan, Hsueh-Fen
AU  - Juan HF
AD  - Department of Life Science, National Taiwan University, Taipei, Taiwan.
FAU - Chen, Ying-Lin
AU  - Chen YL
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Chen, Yi-Chun
AU  - Chen YC
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taipei, Taiwan.
FAU - Lin, Chih-Hsin
AU  - Lin CH
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taipei, Taiwan.
FAU - Lee, Li-Ching
AU  - Lee LC
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Lee, Chi-Mei
AU  - Lee CM
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Lee-Chen, Guey-Jen
AU  - Lee-Chen GJ
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Lai, Yun-Ju
AU  - Lai YJ
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Wu, Yih-Ru
AU  - Wu YR
AD  - Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University 
      College of Medicine, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140716
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (F-Box Proteins)
RN  - 0 (FBXO7 protein, human)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/toxicity
MH  - Adult
MH  - Amino Acid Sequence
MH  - Animals
MH  - Case-Control Studies
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/genetics
MH  - F-Box Proteins/chemistry/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Genetic Predisposition to Disease/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Parkinson Disease/*genetics/metabolism/pathology
MH  - *Polymorphism, Single Nucleotide
MH  - Protective Factors
MH  - Protein Stability
MH  - Protein Structure, Secondary
MH  - Sequence Homology, Amino Acid
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Ubiquitination/drug effects/genetics
MH  - Young Adult
PMC - PMC4100735
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/07/17 06:00
MHDA- 2015/03/10 06:00
PMCR- 2014/07/16
CRDT- 2014/07/17 06:00
PHST- 2014/01/29 00:00 [received]
PHST- 2014/06/06 00:00 [accepted]
PHST- 2014/07/17 06:00 [entrez]
PHST- 2014/07/17 06:00 [pubmed]
PHST- 2015/03/10 06:00 [medline]
PHST- 2014/07/16 00:00 [pmc-release]
AID - PONE-D-14-04425 [pii]
AID - 10.1371/journal.pone.0101392 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 16;9(7):e101392. doi: 10.1371/journal.pone.0101392. 
      eCollection 2014.