Abstract:
:The tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-alpha gene expression. In LPS-stimulated macrophages, the ERK substrates Ets and Elk-1 bind to the TNF-alpha promoter in vivo. Strikingly, Ets and Elk-1 bind to two TNF-alpha nuclear factor of activated T cells (NFAT)-binding sites, which are required for calcineurin and NFAT-dependent TNF-alpha gene expression in lymphocytes. The transcription factors ATF-2, c-jun, Egr-1, and Sp1 are also inducibly recruited to the TNF-alpha promoter in vivo, and the binding sites for each of these activators are required for LPS-stimulated TNF-alpha gene expression. Furthermore, assembly of the LPS-stimulated TNF-alpha enhancer complex is dependent upon the coactivator proteins CREB binding protein and p300. The finding that a distinct set of transcription factors associates with a fixed set of binding sites on the TNF-alpha promoter in response to LPS stimulation lends new insights into the mechanisms by which complex patterns of gene regulation are achieved.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Tsai EY,Falvo JV,Tsytsykova AV,Barczak AK,Reimold AM,Glimcher LH,Fenton MJ,Gordon DC,Dunn IF,Goldfeld AEdoi
10.1128/mcb.20.16.6084-6094.2000subject
Has Abstractpub_date
2000-08-01 00:00:00pages
6084-94issue
16eissn
0270-7306issn
1098-5549journal_volume
20pub_type
杂志文章abstract::We have combined in vitro DNA replication reactions and immunological techniques to analyze biochemical interactions between simian virus (SV40) large T antigen and components of the cellular replication apparatus. First, in vitro SV40 DNA replication was characterized with specific origin mutants. Next, monoclonal an...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.11.4077
更新日期:1986-11-01 00:00:00
abstract::Mutations induced by UVB (313-nm) radiation, a wavelength in the region of peak effectiveness for sunlight-induced skin cancer in humans, have been analyzed at the sequence level in simian cells by using a plasmid shuttle vector (pZ189). We find that significant differences exist between the types of mutations induced...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.12.5425
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.11.9.4572
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5396
更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1988-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2000-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2006-04-01 00:00:00