PubMed_ArguminSci  

PubMed:27798112 JSONTXT 6 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 139-263 DRI_Background denotes Parkinson's disease (PD) is characterized by slow, progressive degeneration of dopaminergic neurons in the substantia nigra.
T2 264-413 DRI_Background denotes The cause of neuronal death in PD is largely unknown, but several genetic loci, including leucine-rich repeat kinase 2 (LRRK2), have been identified.
T3 414-558 DRI_Background denotes LRRK2 has guanosine triphosphatase (GTPase) and kinase activities, and mutations in LRRK2 are the major cause of autosomal-dominant familial PD.
T4 559-715 DRI_Background denotes Histone deacetylases (HDACs) remove acetyl groups from lysine residues on histone tails, promoting transcriptional repression via condensation of chromatin.
T5 716-837 DRI_Outcome denotes Here, we demonstrate that LRRK2 binds to and directly phosphorylates HDAC3 at Ser-424, thereby stimulating HDAC activity.
T6 838-961 DRI_Background denotes Specifically, LRRK2 promoted the deacetylation of Lys-5 and Lys-12 on histone H4, causing repression of gene transcription.
T7 962-1076 DRI_Background denotes Moreover, LRRK2 stimulated nuclear translocation of HDAC3 via the phoshorylation of karyopherin subunit α2 and α6.
T8 1077-1196 DRI_Background denotes HDAC3 phosphorylation and its nuclear translocation were increased in response to 6-hydroxydopamine (6-OHDA) treatment.
T9 1197-1304 DRI_Outcome denotes LRRK2 also inhibited myocyte-specific enhancer factor 2D activity, which is required for neuronal survival.
T10 1391-1550 DRI_Background denotes These findings suggest that LRRK2 affects epigenetic histone modification and neuronal survival by facilitating HDAC3 activity and regulating its localization.