PMID- 18048358
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20210308
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 6
DP  - 2008 Feb 8
TI  - Extracellular signal-regulated kinase regulation of tumor necrosis factor-alpha 
      mRNA nucleocytoplasmic transport requires TAP-NxT1 binding and the AU-rich 
      element.
PG  - 3191-3199
LID - S0021-9258(20)69781-2 [pii]
LID - 10.1074/jbc.M705575200 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) production is regulated by 
      transcriptional and posttranscriptional mechanisms. Lipopolysaccharide activates 
      the NFkappaB pathway increasing TNF-alpha transcription. Lipopolysaccharide also 
      activates the mitogen-activated protein kinase pathways, resulting in 
      stabilization and enhanced translation of the TNF-alpha message. In addition, 
      nuclear export of the TNF-alpha mRNA is a posttranscriptionally regulated process 
      involving the Tpl2-ERK pathway and requiring the presence of the TNF-alpha 
      AU-rich element (ARE). We demonstrate that nuclear export of the TNF-alpha 
      message requires not only the TNF-alpha ARE but also the interaction of the 
      proteins TAP and NxT1, both of which are involved in nucleocytoplasmic transport 
      of mRNA. Through the use of dominant negative ERK1 and ERK2, we establish that 
      control of TNF-alpha mRNA nuclear export operates specifically through ERK1. 
      Finally, we examined the role of two established TNF-alpha ARE-binding proteins, 
      HuR and tristetraprolin, that shuttle between the nucleus and cytoplasm. These 
      data demonstrate that neither tristetraprolin nor HuR is required for TNF-alpha 
      mRNA export. It is unclear at this time if ARE-binding protein(s) directly 
      interact with the TAP-NxT1 complex, if each complex is independently targeted by 
      ERK1, or if only one complex is targeted.
FAU - Skinner, Stephen J
AU  - Skinner SJ
AD  - Veterans Affairs Medical Center, White River Junction, Vermont 05009.
FAU - Deleault, Kristen M
AU  - Deleault KM
AD  - Department of Medicine, Dartmouth Medical School, Dartmouth College, Lebanon, New 
      Hampshire 03756.
FAU - Fecteau, Ryan
AU  - Fecteau R
AD  - Department of Medicine, Dartmouth Medical School, Dartmouth College, Lebanon, New 
      Hampshire 03756.
FAU - Brooks, Seth A
AU  - Brooks SA
AD  - Veterans Affairs Medical Center, White River Junction, Vermont 05009; Department 
      of Medicine, Dartmouth Medical School, Dartmouth College, Lebanon, New Hampshire 
      03756; Department of Microbiology and Immunology, Dartmouth College, Lebanon, New 
      Hampshire 03756. Electronic address: seth.brooks@dartmouth.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071129
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Antigens, Surface)
RN  - 0 (ELAV Proteins)
RN  - 0 (ELAV-Like Protein 1)
RN  - 0 (ELAVL1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Nucleocytoplasmic Transport Proteins)
RN  - 0 (Nxt1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Tap1 protein, mouse)
RN  - 0 (Tristetraprolin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP-Binding Cassette Transporters/*metabolism
MH  - *Active Transport, Cell Nucleus
MH  - Animals
MH  - Antigens, Surface/chemistry
MH  - Base Sequence
MH  - ELAV Proteins
MH  - ELAV-Like Protein 1
MH  - *Extracellular Signal-Regulated MAP Kinases
MH  - *Gene Expression Regulation
MH  - Mice
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - Nucleocytoplasmic Transport Proteins/*metabolism
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/chemistry
MH  - Tristetraprolin/chemistry
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2007/12/01 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - S0021-9258(20)69781-2 [pii]
AID - 10.1074/jbc.M705575200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Feb 8;283(6):3191-3199. doi: 10.1074/jbc.M705575200. Epub 2007 
      Nov 29.