Sequestosome1/p62: A regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth

Article ID	Journal	Published Year	Pages	File Type
8270639	Free Radical Biology and Medicine	2013	15 Pages	PDF

Abstract

A stress-inducible protein sequestosome1 (SQSTM1) regulates H2O2-driven intracellular signaling pathways, including proliferation and migration of arterial smooth muscle cells, Th2 skewing T cell differentiation, and NGF-induced neurite outgrowth in PC12 cells. SQSTM1 regulates redox sensitive voltage-activated potassium (Kv) channels as a functional partner of atypical PKCs and tyrosine kinase p56Lck through two different signaling axes, PKCÎ¶-SQSTM1-KvÎ² and SQSTM1-Lck-Dlgh1-KvÎ±1.3. We discuss the hypothesis that SQSTM1 modulates interaction of Kv1.3 with Î²1 integrin, which plays a critical role in biological responses via these signaling axes.196

Keywords

SQSTM1 p62 HNE Heme oxygenase-1 ZIP TxA2 SMCs LCK aPKC oxLDL Th2 T helper 2 NF-κB UBA PASMCs arterial smooth muscle cells Kelch-like ECH associated protein 1 Protein kinase C zeta PRX1 p56Lck sequestosome1 SAP97 PKCζ synapse-associated protein 97 PDB AP-1 CDK Nrf2 EGF NGF 4-hydroxynonenal HO-1 TCr IL-1 keap1 ERK1/2 MAPK ROS interleukin-1 Thromboxane A2 Neurite outgrowth pulmonary artery smooth muscle cells Smooth muscle cells epidermal growth factor antioxidant response element nerve growth factor nuclear factor erythroid 2-related factor 2 nuclear factor kappa beta T lymphocytes oxidized low density lipoprotein ARE Neointimal hyperplasia Peroxiredoxin 1 activator protein-1 atypical protein kinase C mitogen-activated protein kinase Kv channels Voltage-gated potassium channel extracellular regulated kinase 1/2 cyclin-dependent kinase Reactive oxygen species T cell receptor