Neurosci Lett 2009,
PMID: 19010391
Heo, Seong Ryong; Han, Ah Mi; Kwon, Yunhee Kim; Joung, Insil
The p62 protein has been identified as a major component of the protein aggregations associated with neurodegenerative disease. Oxidative insult has also been identified as a principal cause of neurodegenerative disease. Thus, in the present study, we investigated the potential role of p62 in oxidative stress-induced cell death in SH-SY5Y human neuroblastoma cells. The results indicated that H(2)O(2) treatment induced p62 expression in SH-SY5Y cells. In addition, p62 showed neuroprotective effects against H(2)O(2)-induced cell death in differentiated SH-SY5Y cells. p62 expression prolonged Akt phosphorylation during the later stages of H(2)O(2)-induced cell death. Furthermore, coexpression of p62 and wild-type PDK1, the upstream kinase of Akt, further increased Akt phosphorylation and cell viability, whereas the expression of kinase-defective PDK1 reversed the cytoprotective effects of p62 under oxidative stress. Overexpression of p62 led to the dissociation of PDK1 from the 14-3-3theta protein, which is thought to be a negative regulator of PDK1 kinase activity. These findings suggest a mechanism that involves the p62-mediated modulation of the interaction between signaling molecules and results in cell survival.
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Text Mining Data
Akt → PDK1: "
Furthermore, coexpression of p62 and wild-type
PDK1 , the upstream kinase of Akt, further
increased Akt phosphorylation and cell viability, whereas the expression of kinase-defective PDK1 reversed the cytoprotective effects of p62 under oxidative stress
"
Manually curated Databases
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IRef Biogrid Interaction:
YWHAQ
—
LCK
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
YWHAQ
—
PDPK1
(physical association, affinity chromatography technology)
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IRef Hprd Interaction:
YWHAQ
—
PDK1
(in vivo)
In total, 3 gene pairs are associated to this article in curated databases