RGD Reference Report - The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death. - Rat Genome Database

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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.
RGD ID: 8693407
Pubmed: PMID:21715626   (View Abstract at PubMed)
PMCID: PMC6623145   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0035-11.2011   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cellular process  IMP 8693407hippocampal neuronsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Abl1  (ABL proto-oncogene 1, non-receptor tyrosine kinase)


Additional Information