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Nuclear Translocation of p65 is Controlled by Sec6 via the Degradation of IκBα
Author(s) -
Tanaka Toshiaki,
Iino Mitsuyoshi
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25122
Subject(s) - ribosomal s6 kinase , microbiology and biotechnology , biology , signal transduction , kinase , mapk/erk pathway , small interfering rna , creb , iκbα , transcription factor , nf κb , cancer research , transfection , cell culture , biochemistry , genetics , pi3k/akt/mtor pathway , gene , p70 s6 kinase 1
Nuclear factor‐κB (NF‐κB) is an inducible transcription factor that mediates immune and inflammatory responses. NF‐κB pathways are also involved in cell adhesion, differentiation, proliferation, autophagy, senescence, and protection against apoptosis. The deregulation of NF‐κB activity is found in a number of disease states, including cancer, arthritis, chronic inflammation, asthma, neurodegenerative diseases, and heart disease. The 90 kDa ribosomal S6 kinase (p90RSK) family, which is serine/threonine kinases, is phosphorylated by extracellular signal‐regulated kinase1/2 (ERK1/2) and is related to NF‐κB pathways. Our previous studies revealed that Sec6, a component of the exocyst complex, plays specific roles in cell–cell adhesion and cell cycle arrest. However, the mechanism by which Sec6 regulates the NF‐κB signaling pathway is unknown. We demonstrated that Sec6 knockdown inhibited the degradation of IκBα and delayed the nucleus‐cytoplasm translocation of p65 in HeLa cells transfected with Sec6 siRNAs after treatment with tumor necrosis factor alpha (TNF‐α). Furthermore, the binding of p65 and cAMP response element binding protein (CREB) binding protein (CBP) or p300 decreased and NF‐κB related genes which were inhibitors of NF‐κB alpha (IκBα), A20, B cell lymphoma protein 2 (Bcl‐2), and monocyte chemoattractant protein‐1 (MCP‐1) were low in cells transfected with Sec6 siRNAs in response to TNF‐α stimulation. Sec6 knockdown decreased the expression of p90RSKs and the phosphorylation of ERK or p90RSK1 at Ser380 or IκBα at Ser32. The present study suggests that Sec6 regulates NF‐κB transcriptional activity via the control of the phosphorylation of IκBα, p90RSK1, and ERK. J. Cell. Physiol. 231: 719–730, 2016. © 2015 Wiley Periodicals, Inc.