Nuclear Translocation of p65 is Controlled by Sec6 via the Degradation of IB

作者：Tanaka Toshiaki^*; Iino Mitsuyoshi

来源：Journal of Cellular Physiology, 2016, 231(3): 719-730.

DOI：10.1002/jcp.25122

Nuclear factor-B (NF-B) is an inducible transcription factor that mediates immune and inflammatory responses. NF-B pathways are also involved in cell adhesion, differentiation, proliferation, autophagy, senescence, and protection against apoptosis. The deregulation of NF-B activity is found in a number of disease states, including cancer, arthritis, chronic inflammation, asthma, neurodegenerative diseases, and heart disease. The 90kDa 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-B 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-B signaling pathway is unknown. We demonstrated that Sec6 knockdown inhibited the degradation of IB and delayed the nucleus-cytoplasm translocation of p65 in HeLa cells transfected with Sec6 siRNAs after treatment with tumor necrosis factor alpha (TNF-). Furthermore, the binding of p65 and cAMP response element binding protein (CREB) binding protein (CBP) or p300 decreased and NF-B related genes which were inhibitors of NF-B alpha (IB), 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- stimulation. Sec6 knockdown decreased the expression of p90RSKs and the phosphorylation of ERK or p90RSK1 at Ser380 or IB at Ser32. The present study suggests that Sec6 regulates NF-B transcriptional activity via the control of the phosphorylation of IB, p90RSK1, and ERK. J. Cell. Physiol. 231: 719-730, 2016.

• 出版日期2016-3