PMID- 7982959
OWN - NLM
STAT- MEDLINE
DCOM- 19941230
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 48
DP  - 1994 Dec 2
TI  - The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene 
      transcription.
PG  - 30445-50
AB  - The tumor necrosis factor-alpha (TNF alpha) gene is an immediate early gene in 
      activated T cells, in that it is rapidly induced without a requirement for 
      protein synthesis. Maximal induction of TNF alpha mRNA can be induced by 
      treatment of T cells with calcium ionophores alone, via a calcineurin-dependent 
      process that is blocked by cyclosporin A. We have previously identified a 
      promoter element, kappa 3, that is required for calcium-stimulated, cyclosporin 
      A-sensitive induction of the TNF alpha gene in activated T cells. Here, we 
      demonstrate that the kappa 3 binding factor contains NFATp, a 
      cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene 
      transcription. NFATp binds to two sites within the kappa 3 element, and occupancy 
      of both sites is required for TNF alpha gene induction. Thus, although the kappa 
      3 element has little sequence similarity to other NFATp-binding sites, it appears 
      to function as a cyclosporin-sensitive promoter element in T cells by virtue of 
      its ability to bind NFATp. The involvement of NFATp in transcriptional activation 
      of both the interleukin-2 and TNF alpha genes suggests that this factor plays an 
      important role in the coordinate induction of multiple cytokine genes, starting 
      at the earliest stages of T cell activation.
FAU - McCaffrey, P G
AU  - McCaffrey PG
AD  - Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 
      02115.
FAU - Goldfeld, A E
AU  - Goldfeld AE
FAU - Rao, A
AU  - Rao A
LA  - eng
GR  - CA-42471/CA/NCI NIH HHS/United States
GR  - CA-58735/CA/NCI NIH HHS/United States
GR  - GM-46227/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
GS  - v-fos
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Nucleus/metabolism
MH  - Cell Transformation, Neoplastic
MH  - Clone Cells
MH  - Cyclosporine/*pharmacology
MH  - Cytosol/metabolism
MH  - DNA-Binding Proteins/isolation & purification/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Genes, fos
MH  - Humans
MH  - Interleukin-2/biosynthesis
MH  - Molecular Sequence Data
MH  - NFATC Transcription Factors
MH  - Nuclear Proteins/metabolism
MH  - Oligodeoxyribonucleotides
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - T-Lymphocytes
MH  - Transcription Factors/isolation & purification/*metabolism
MH  - Transcription, Genetic/drug effects/*physiology
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
EDAT- 1994/12/02 00:00
MHDA- 1994/12/02 00:01
CRDT- 1994/12/02 00:00
PHST- 1994/12/02 00:00 [pubmed]
PHST- 1994/12/02 00:01 [medline]
PHST- 1994/12/02 00:00 [entrez]
AID - S0021-9258(18)43833-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Dec 2;269(48):30445-50.