scholarly journals Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp.

1996 ◽  
Vol 16 (2) ◽  
pp. 459-467 ◽  
Author(s):  
E Y Tsai ◽  
J Jain ◽  
P A Pesavento ◽  
A Rao ◽  
A E Goldfeld
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Gene Transcription ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor

The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest genes expressed upon the activation of a T or B cell through its antigen receptor. Previous experiments have demonstrated that in stimulated T cells, a TNF-alpha promoter element, kappa 3, which binds NFATp, is required for the cyclosporin A-sensitive transcriptional activation of the gene. Here, we demonstrate that a cyclic AMP response element (CRE), which lies immediately upstream of the kappa 3 site, is also required for induction of TNF-alpha gene transcription in T cells stimulated by calcium ionophore or T-cell receptor ligands. The CRE binds ATF-2 and Jun proteins in association with NFATp bound to kappa 3. These proteins bind noncooperatively in vitro; however, the transcriptional activity of the CRE/kappa 3 composite site is dramatically higher than the activity of the kappa 3 site alone, indicating that the two sites cooperate in vivo. This study is the first demonstration of a role for ATF-2 in TNF-alpha gene transcription and of a functional interaction between ATF-2/Jun and NFATp. This novel pairing of NFATp with ATF-2/Jun may account for the specific and immediate pattern of TNF-alpha gene transcription in stimulated T cells.

scholarly journals 2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

1996 ◽  
Vol 16 (6) ◽  
pp. 2814-2822 ◽  
Author(s):  
N Jarrous ◽  
F Osman ◽  
R Kaempfer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Translation Initiation Factor ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Rnase Protection ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor

2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid cells. 2-AP does not inhibit transcription of the human TNF-alpha gene, nor does it affect mRNA stability. Instead, the flow of short-lived precursor transcripts into mature TNF-alpha mRNA is blocked. When 2-AP is present during induction, unspliced TNF-alpha precursor transcripts accumulate at the expense of mRNA. Using RNase protection analysis with genomic probes for different exon-intron junctions, we show that 2-AP blocks splicing of TNF-alpha mRNA. Neither the TNF-beta nor the interleukin-1 beta gene shows such regulation. 2-AP also inhibits splicing of precursor RNA transcribed from an exogenous human TNF-alpha gene. Sequences within this gene thus confer sensitivity to 2-AP. Yet, control is not exerted at a specific splice site. Our results reveal the involvement of a 2-AP-sensitive component, expressed in functional form before induction, in the splicing of TNF-alpha mRNA.

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer

2021 ◽  
Vol 48 (2) ◽  
pp. 1433-1437
Author(s):  
Negin Behboodi ◽  
Marjaneh Farazestanian ◽  
Azam Rastgar-Moghadam ◽  
Mehrane Mehramiz ◽  
Ehsan Karimi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Alpha Gene ◽  
Necrosis Factor
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