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P62 binding to protein kinase C ? regulates tumor necrosis factor ?-induced apoptotic pathway in endothelial cells.


ABSTRACT: Protein kinase C (PKC) ? is a key pathological mediator of endothelial cell apoptosis. p62 is a scaffold protein that regulates several cell signaling pathways by binding to target proteins. Because PKC? and p62 contain Phox/Bem1p (PB1) modules that mediate protein-protein interactions, we hypothesized that an interaction between p62 and PKC? is required for tumor necrosis factor ?-induced PKC? signaling in endothelial cells.In human umbilical vein endothelial cell, tumor necrosis factor ? (10 ng/mL) enhanced the interaction between p62 and PKC?. Transfection with p62 small interfering RNA reduced the activation of both PKC? and its downstream targets JNK and caspase 3, suggesting that p62 is necessary for PKC? signaling. Overexpression of only the PB1 domain of p62 inhibited p62-PKC? interaction, showing that binding of these 2 proteins is mediated by their PB1 domains. Furthermore, overexpression of the p62 PB1 domain suppressed tumor necrosis factor ?-induced PKC? activation and subsequent activation of JNK and caspase 3. Finally, transfection of either p62 small interfering RNA or the PB1 domain of p62 inhibited human umbilical vein endothelial cell apoptosis.Our results suggest a novel function of p62 that regulates the activity of PKC? by binding to PKC?, thereby activating the PKC?-JNK-caspase 3 apoptotic pathway in endothelial cells.

SUBMITTER: Kim GY 

PROVIDER: S-EPMC4084716 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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p62 binding to protein kinase C ζ regulates tumor necrosis factor α-induced apoptotic pathway in endothelial cells.

Kim Geun-Young GY   Nigro Patrizia P   Fujiwara Keigi K   Abe Jun-ichi J   Berk Bradford C BC  

Arteriosclerosis, thrombosis, and vascular biology 20120927 12


<h4>Objective</h4>Protein kinase C (PKC) ζ is a key pathological mediator of endothelial cell apoptosis. p62 is a scaffold protein that regulates several cell signaling pathways by binding to target proteins. Because PKCζ and p62 contain Phox/Bem1p (PB1) modules that mediate protein-protein interactions, we hypothesized that an interaction between p62 and PKCζ is required for tumor necrosis factor α-induced PKCζ signaling in endothelial cells.<h4>Methods and results</h4>In human umbilical vein e  ...[more]

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