In vivo regulation of interleukin-2 receptor alpha gene transcription by the coordinated binding of constitutive and inducible factors in human primary T cells.

1995 ◽  
Vol 14 (20) ◽  
pp. 5060-5072 ◽  
Author(s):  
M. Algarté ◽  
P. Lécine ◽  
R. Costello ◽  
A. Plet ◽  
D. Olive ◽  
...  
Keyword(s):  
T Cells ◽  
Gene Transcription ◽  
Interleukin 2 ◽  
Receptor Alpha ◽  
Interleukin 2 Receptor ◽  
Alpha Gene

scholarly journals Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene.

1996 ◽  
Vol 16 (12) ◽  
pp. 6829-6840 ◽  
Author(s):  
P Lécine ◽  
M Algarté ◽  
P Rameil ◽  
C Beadling ◽  
P Bucher ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Critical Element ◽  
Regulatory Regions ◽  
Receptor Alpha ◽  
Interleukin 2 Receptor ◽  
High Affinity Receptor ◽  
Alpha Gene ◽  
In Vivo Footprinting

The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor.

scholarly journals Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel.

1992 ◽  
Vol 12 (9) ◽  
pp. 4067-4075 ◽  
Author(s):  
T H Tan ◽  
G P Huang ◽  
A Sica ◽  
P Ghosh ◽  
H A Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Interleukin 2 ◽  
Regulatory Elements ◽  
Chain Gene ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Alpha Gene ◽  
Receptor Alpha Chain

The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation.

Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel

1992 ◽  
Vol 12 (9) ◽  
pp. 4067-4075
Author(s):  
T H Tan ◽  
G P Huang ◽  
A Sica ◽  
P Ghosh ◽  
H A Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Interleukin 2 ◽  
Regulatory Elements ◽  
Chain Gene ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Alpha Gene ◽  
Receptor Alpha Chain

The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation.

Interaction between NF-kappa B- and serum response factor-binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes

1993 ◽  
Vol 13 (4) ◽  
pp. 2536-2545
Author(s):  
A A Kuang ◽  
K D Novak ◽  
S M Kang ◽  
K Bruhn ◽  
M J Lenardo
Keyword(s):  
T Cells ◽  
Serum Response Factor ◽  
Interleukin 2 ◽  
Response Factor ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Serum Response ◽  
Receptor Alpha Chain

We find that a short enhancer element containing the NF-kappa B binding site from the interleukin-2 receptor alpha-chain gene (IL-2R alpha) is preferentially activated in T cells. The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone. Serum response factor (SRF) binds to a site adjacent to the NF-kappa B site in the IL-2R enhancer, and both sites together have strong transcriptional activity specifically in T cells. Surprisingly, the levels of SRF constitutively expressed in T cells are consistently higher than in other cell types. Overexpression of SRF in B cells causes the IL-2R enhancer to function as well as it does in T cells, suggesting that the high level of SRF binding in T cells is functionally important.

scholarly journals Interaction between NF-kappa B- and serum response factor-binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes.

1993 ◽  
Vol 13 (4) ◽  
pp. 2536-2545 ◽  
Author(s):  
A A Kuang ◽  
K D Novak ◽  
S M Kang ◽  
K Bruhn ◽  
M J Lenardo
Keyword(s):  
T Cells ◽  
Serum Response Factor ◽  
Interleukin 2 ◽  
Response Factor ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Serum Response ◽  
Receptor Alpha Chain

We find that a short enhancer element containing the NF-kappa B binding site from the interleukin-2 receptor alpha-chain gene (IL-2R alpha) is preferentially activated in T cells. The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone. Serum response factor (SRF) binds to a site adjacent to the NF-kappa B site in the IL-2R enhancer, and both sites together have strong transcriptional activity specifically in T cells. Surprisingly, the levels of SRF constitutively expressed in T cells are consistently higher than in other cell types. Overexpression of SRF in B cells causes the IL-2R enhancer to function as well as it does in T cells, suggesting that the high level of SRF binding in T cells is functionally important.

The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV

Cell ◽  
1988 ◽  
Vol 53 (5) ◽  
pp. 827-836 ◽  
Author(s):  
Ernst Böhnlein ◽  
John W. Lowenthal ◽  
Miriam Siekevitz ◽  
Dean W. Ballard ◽  
B.Robert Franza ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Nuclear Proteins ◽  
Receptor Alpha ◽  
Interleukin 2 Receptor ◽  
Alpha Gene ◽  
Mitogen Activation

Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T cells by administration of humanized anti-Tac antibody to patients with psoriasis

2000 ◽  
Vol 43 (3) ◽  
pp. 448-458 ◽  
Author(s):  
James G. Krueger ◽  
Ian B. Walters ◽  
Megumi Miyazawa ◽  
Patricia Gilleaudeau ◽  
John Hakimi ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
High Affinity ◽  
Interleukin 2 Receptor

scholarly journals Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene.

1997 ◽  
Vol 17 (4) ◽  
pp. 2351-2351 ◽  
Author(s):  
P Lécine ◽  
M Algarté ◽  
P Rameil ◽  
C Beadling ◽  
P Bucher ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Critical Element ◽  
Receptor Alpha ◽  
Interleukin 2 Receptor ◽  
Alpha Gene
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