Unknown

Dataset Information

0

Glycogen synthase kinase 3? suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity.

ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the N-terminal of huntingtin. The amount of aggregate-prone protein is controlled by various mechanisms, including molecular chaperones. Vaccinia-related kinase 2 (VRK2) is known to negatively regulate chaperonin TRiC, and VRK2-facilitated degradation of TRiC increases polyQ protein aggregation, which is involved in HD. We found that VRK2 activity was negatively controlled by glycogen synthase kinase 3? (GSK3?). GSK3? directly bound to VRK2 and inhibited the catalytic activity of VRK2 in a kinase activity-independent manner. Furthermore, GSK3? increased the stability of TRiC and decreased the formation of HttQ103-GFP aggregates by inhibiting VRK2. These results indicate that GSK3? signaling may be a regulatory mechanism of HD progression and suggest targets for further therapeutic trials for HD.

SUBMITTER: Lee E 

PROVIDER: S-EPMC4932512 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Glycogen synthase kinase 3β suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity.

Lee Eunju E   Ryu Hye Guk HG   Kim Sangjune S   Lee Dohyun D   Jeong Young-Hun YH   Kim Kyong-Tai KT  

Scientific reports 20160705

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the N-terminal of huntingtin. The amount of aggregate-prone protein is controlled by various mechanisms, including molecular chaperones. Vaccinia-related kinase 2 (VRK2) is known to negatively regulate chaperonin TRiC, and VRK2-facilitated degradation of TRiC increases polyQ protein aggregation, which is involved in HD. We found that VRK2 activity was negatively controlled by gly  ...[more]

Similar Datasets

Unknown Helicobacter pylori suppresses glycogen synthase kinase 3beta to promote beta-catenin activity.
| S-EPMC2662023 | biostudies-literature
Unknown Lithium suppresses astrogliogenesis by neural stem and progenitor cells by inhibiting STAT3 pathway independently of glycogen synthase kinase 3 beta.
| S-EPMC3170293 | biostudies-literature
Unknown Luteolin suppresses cancer cell proliferation by targeting vaccinia-related kinase 1.
| S-EPMC4195671 | biostudies-literature
Unknown Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via negative regulation of the chaperonin TRiC.
| S-EPMC3911496 | biostudies-literature
Unknown Resibufogenin suppresses transforming growth factor-β-activated kinase 1-mediated nuclear factor-κB activity through protein kinase C-dependent inhibition of glycogen synthase kinase 3.
| S-EPMC6215888 | biostudies-literature
Unknown Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer.
| S-EPMC2647811 | biostudies-literature
Unknown Activity-dependent regulation of dendritic growth and maintenance by glycogen synthase kinase 3?.
| S-EPMC3821971 | biostudies-literature
Unknown In vivo regulation of glycogen synthase kinase 3? activity in neurons and brains.
| S-EPMC5561119 | biostudies-literature
Unknown Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression.
| S-EPMC6635502 | biostudies-literature
Unknown Interactomes of Glycogen Synthase Kinase-3 Isoforms.
| S-EPMC9990120 | biostudies-literature