Regulation of the proteasome by AMPK in endothelial cells: the role of O-GlcNAc transferase (OGT).

PloS One
Jian XuMing-Hui Zou

Abstract

26S proteasome is a macromolecular multi-subunit complex responsible for recognizing, unfolding, and ultimately destroying proteins. It remains poorly understood how 26S proteasome activity is regulated. The present study was to investigate if AMP-activated protein kinase (AMPK) functions as a physiological suppressor of the 26S proteasome in endothelial cells. 26S proteasome assembly, activity, and O-GlcNAcylation of P700 were assayed in cultured human umbilical vein endothelial cells (HUVEC) and mouse aortas isolated from C57BL6 wild type and AMPKα2 knockout mice with or without being exposed to selective AMPK activators or inhibitors. Pharmacological and genetic activation of AMPK effectively suppresses 26S proteasomes in endothelial cells. Conversely, inactivation of AMPK either pharmacologically or genetically increases 26S proteasome activity; furthermore, the inactivation decreases the O-GlcNAcylation of PA700/S10B (the regulatory complex in 26S proteasomes) and increases the assembly of 26S proteasomes. In contrast, AMPK activation increases levels of O-GlcNAcylated PA700/S10B, likely through enhanced association of PA700 with O-GlcNAc transferase (OGT), the enzyme that catalyzes protein O-GlcNAcylation. Finally, aortas...Continue Reading

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Citations

Jan 21, 2014·Antioxidants & Redox Signaling·Silke MeinersAnne Caniard
Mar 18, 2015·Molecular Medicine Reports·Peng LuoGang Li
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Oct 20, 2018·Frontiers in Cell and Developmental Biology·Nur Mehpare Kocaturk, Devrim Gozuacik

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Methods Mentioned

BETA
transfection
co-immunoprecipitation

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