PMID- 26247921
OWN - NLM
STAT- MEDLINE
DCOM- 20160322
LR  - 20230120
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 231
IP  - 3
DP  - 2016 Mar
TI  - Nuclear Translocation of p65 is Controlled by Sec6 via the Degradation of IkappaBalpha.
PG  - 719-30
LID - 10.1002/jcp.25122 [doi]
AB  - Nuclear factor-kappaB (NF-kappaB) is an inducible transcription factor that mediates 
      immune and inflammatory responses. NF-kappaB pathways are also involved in cell 
      adhesion, differentiation, proliferation, autophagy, senescence, and protection 
      against apoptosis. The deregulation of NF-kappaB 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-kappaB 
      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-kappaB signaling pathway is 
      unknown. We demonstrated that Sec6 knockdown inhibited the degradation of IkappaBalpha 
      and delayed the nucleus-cytoplasm translocation of p65 in HeLa cells transfected 
      with Sec6 siRNAs after treatment with tumor necrosis factor alpha (TNF-alpha). 
      Furthermore, the binding of p65 and cAMP response element binding protein (CREB) 
      binding protein (CBP) or p300 decreased and NF-kappaB related genes which were 
      inhibitors of NF-kappaB alpha (IkappaBalpha), 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-alpha stimulation. Sec6 knockdown decreased the 
      expression of p90RSKs and the phosphorylation of ERK or p90RSK1 at Ser380 or IkappaBalpha 
      at Ser32. The present study suggests that Sec6 regulates NF-kappaB transcriptional 
      activity via the control of the phosphorylation of IkappaBalpha, p90RSK1, and ERK.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Tanaka, Toshiaki
AU  - Tanaka T
AD  - Department of Anatomy and Cell Biology, School of Medicine, Yamagata University, 
      2-2-2 Iidanishi, Yamagata, Japan.
AD  - Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and 
      Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, 
      Yamagata, Japan.
FAU - Iino, Mitsuyoshi
AU  - Iino M
AD  - Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and 
      Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, 
      Yamagata, Japan.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (EXOC3 protein, human)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vesicular Transport Proteins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Down-Regulation/physiology
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - I-kappa B Proteins/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - Phosphorylation
MH  - Protein Transport/genetics/physiology
MH  - Signal Transduction/genetics/physiology
MH  - Transcription Factor RelA/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vesicular Transport Proteins/*metabolism
EDAT- 2015/08/08 06:00
MHDA- 2016/03/24 06:00
CRDT- 2015/08/07 06:00
PHST- 2015/05/13 00:00 [received]
PHST- 2015/08/04 00:00 [accepted]
PHST- 2015/08/07 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
AID - 10.1002/jcp.25122 [doi]
PST - ppublish
SO  - J Cell Physiol. 2016 Mar;231(3):719-30. doi: 10.1002/jcp.25122.