Parkin is not regulated by the unfolded protein response in human neuroblastoma cells.
Mutations in the parkin gene cause the majority of cases of familial-linked Parkinson's disease, and mounting evidence suggests that parkin may play a role in idiopathic disease. Previous reports suggest that parkin may respond to and relieve, via E3-ligase activity, cellular stress at the endoplasmic reticulum caused by the accumulation of unfolded proteins. However, parkin's relationship to the mammalian unfolded protein response is unclear. Here, we comprehensively evaluate endogenous parkin in SH-SY5Y neuroblastomas at the promoter, RNA, and protein levels in response to unfolded protein stress induced by tunicamycin. While we find strong up-regulation of genes linked to the unfolded protein stress pathway, we detect no significant changes in parkin. These data suggest a lack of association between parkin and the unfolded protein response in SH-SY5Y cells.
West
Andrew B
AB
Program for Molecular Neuroscience, Department of Neuroscience, Mayo Clinic Jacksonville, 32224, Jacksonville, FL, USA.
Gonzalez-de-Chavez
Fanny
F
Wilkes
Kristen
K
O'Farrell
Casey
C
Farrer
Matthew J
MJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D017510:Protein Folding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014415:Tunicamycin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D012333:RNA, Messenger; D014415:Tunicamycin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases