International Immunology, Vol. 11, No. 12, 1945-1956,
December 1999
© 1999 Japanese Society for Immunology
Nuclear factor of activated T cells contributes to the function of the CD28 response region of the granulocyte macrophage-colony stimulating factor promoter
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia 5001, Australia
Correspondence to: M. F. Shannon, Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
The granulocyte macrophage colony stimulating factor (GM-CSF) promoter contains a 10 bp element known as CK-1 or CD28RE that specifically responds to the co-stimulatory signal delivered to T cells via the CD28 surface receptor. This element is a variant NF
B site that does not function alone but requires an adjacent promoter region that includes a classical NFB element, an Sp-1 site and a putative activator protein-1 (AP-1)-like binding site. The entire region is referred to as the CD28 response region (CD28RR). The GM-CSF CK-1 element has been shown to bind NFB proteins, in particular c-Rel, whose binding and function is dependent on the architectural transcription factor HMGI(Y). It has been previously suggested that the nuclear factor of activated T cells (NFAT) family of proteins also plays a role in the activity of this region. We show here that recombinant NFATp but not AP-1 can bind to the GM-CSF CD28RR. NFATp present in activated Jurkat T cell extracts can also interact with the CD28RR. The binding of NFATp and Rel proteins requires the same core CK-1 sequences, and appears to be mutually exclusive. We investigated the functional significance of NFATp binding to CK-1 by overexpressing the protein in Jurkat T cells and found that NFATp cannot activate the CD28RR alone but can cooperate with signals generated by phorbol 12-myristate 13-acetate/calcium ionophore. The CD28RR is therefore a complex region that can bind and respond to a combination of transcription factors and signals.
Keywords: co-stimulatory molecules, cytokines, gene regulation, T cell, transcription factors
1 Present address: Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland 4072, Australia
2 Present address: Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. V. Falvo, C. H. Lin, A. V. Tsytsykova, P. K. Hwang, D. Thanos, A. E. Goldfeld, and T. Maniatis A dimer-specific function of the transcription factor NFATp PNAS, December 16, 2008; 105(50): 19637 - 19642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, M. Holm, X.-Q. Xie, M. Wolf-Watz, and T. Grundstrom AML1/Runx1 Recruits Calcineurin to Regulate Granulocyte Macrophage Colony-stimulating Factor by Ets1 Activation J. Biol. Chem., July 9, 2004; 279(28): 29398 - 29408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Melchjorsen, L. N. Sorensen, and S. R. Paludan Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function J. Leukoc. Biol., September 1, 2003; 74(3): 331 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu and T. Grundstrom Calcium Regulation of GM-CSF by Calmodulin-Dependent Kinase II Phosphorylation of Ets1 Mol. Biol. Cell, December 1, 2002; 13(12): 4497 - 4507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sharma, N. Grandvaux, Y. Mamane, P. Genin, N. Azimi, T. Waldmann, and J. Hiscott Regulation of IFN Regulatory Factor 4 Expression in Human T Cell Leukemia Virus-I-Transformed T Cells J. Immunol., September 15, 2002; 169(6): 3120 - 3130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Attema, R. Reeves, V. Murray, I. Levichkin, M. D. Temple, D. J. Tremethick, and M. F. Shannon The Human IL-2 Gene Promoter Can Assemble a Positioned Nucleosome That Becomes Remodeled Upon T Cell Activation J. Immunol., September 1, 2002; 169(5): 2466 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cakouros, P. N. Cockerill, A. G. Bert, R. Mital, D. C. Roberts, and M. F. Shannon A NF-{{kappa}}B/Sp1 Region Is Essential for Chromatin Remodeling and Correct Transcription of a Human Granulocyte- Macrophage Colony-Stimulating Factor Transgene J. Immunol., July 1, 2001; 167(1): 302 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dong, E. Loukinova, Z. Chen, L. Gangi, T. I. Chanturita, E. T. Liu, and C. Van Waes Molecular Profiling of Transformed and Metastatic Murine Squamous Carcinoma Cells by Differential Display and cDNA Microarray Reveals Altered Expression of Multiple Genes Related to Growth, Apoptosis, Angiogenesis, and the NF-{{kappa}}B Signal Pathway Cancer Res., June 1, 2001; 61(12): 4797 - 4808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Shannon, L. S. Coles, J. Attema, and P. Diamond The role of architectural transcription factors in cytokine gene transcription J. Leukoc. Biol., January 1, 2001; 69(1): 21 - 32. [Abstract] [Full Text]
|
|
|
|
|
|
A. G. Bert, J. Burrows, A. Hawwari, M. A. Vadas, and P. N. Cockerill Reconstitution of T Cell-Specific Transcription Directed by Composite NFAT/Oct Elements J. Immunol., November 15, 2000; 165(10): 5646 - 5655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Diamond, M. F. Shannon, M. A. Vadas, and L. S. Coles Cold Shock Domain Factors Activate the Granulocyte-Macrophage Colony-stimulating Factor Promoter in Stimulated Jurkat T Cells J. Biol. Chem., March 9, 2001; 276(11): 7943 - 7951. [Abstract] [Full Text] [PDF]
|
|