Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death.

Authors: Xiao, L  Chen, D  Hu, P  Wu, J  Liu, W  Zhao, Y  Cao, M  Fang, Y  Bi, W  Zheng, Z  Ren, J  Ji, G  Wang, Y  Yuan, Z 
Citation: Xiao L, etal., J Neurosci. 2011 Jun 29;31(26):9611-9. doi: 10.1523/JNEUROSCI.0035-11.2011.
Pubmed: (View Article at PubMed) PMID:21715626
DOI: Full-text: DOI:10.1523/JNEUROSCI.0035-11.2011

Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. The protein kinase MST1 (mammalian Ste20-like kinase 1) plays a major role in oxidative stress-induced cell death in primary mammalian neurons. However, the mechanisms that regulate MST1 in oxidative stress responses remain largely unknown. In the present study, we demonstrate that the protein kinase c-Abl phosphorylates MST1 at Y433, which triggers the stabilization and activation of MST1. Inhibition of c-Abl promotes the degradation of MST1 through C terminus of Hsc70-interacting protein (CHIP)-mediated ubiquitination, and thereby attenuates cell death. Oxidative stress induces the c-Abl-dependent tyrosine phosphorylation of MST1 and increases the interaction between MST1 and FOXO3 (Forkhead box O3), thereby activating the MST1-FOXO signaling pathway, leading to cell death in both primary culture neurons and rat hippocampal neurons. The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST1 suggests that the c-Abl-MST1 signaling cascade plays an important role in cellular responses to oxidative stress.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 8693407
Created: 2014-07-15
Species: All species
Last Modified: 2014-07-15
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.