| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Cell Signaling, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304;
Department of Microbiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; and
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
NFAT regulates transcription of a number of cytokine and other immunoregulatory genes. We have isolated NFATx, which is one of four members of the NFAT family of transcription factors and is preferentially expressed in the thymus and peripheral blood leukocytes, and an isoform of NFATx, NFATx1. Here we provide evidence showing that 15 amino acids in the carboxyl-terminal end of NFATx1 are required for its maximum transactivation activity in Jurkat T cells. A fusion between these 15 amino acids and the GAL4 DNA binding domain was capable of transactivating reporters driven by the GAL4 DNA binding site. Interestingly, this 15-amino acid transactivation sequence is well conserved in NFAT family proteins, although the sequences contiguous to the carboxyl-terminal regions of the NFAT family are much less conserved. We also report three additional isoforms of NFATx, designated NFATx2, NFATx3, and NFATx4. This transactivation sequence is altered by tissue-specific alternative splicing in newly isolated NFATx isoforms, resulting in lower transactivation activity in Jurkat T cells. NFATx1 is expressed predominantly in the thymus and peripheral blood leukocyte, while the skeletal muscle expressed primarily NFATx2. In Jurkat cells, transcription from the NFAT site of the IL-2 promoter is activated strongly by NFATx1 but only weakly by NFATx2. These data demonstrate that the 15-amino acid sequence of NFATx1 is a major transactivation sequence required for induction of genes by NFATx1 in T cells and possibly regulates NFAT activity through tissue-specific alternative splicing.
This article has been cited by other articles:
|
|
 |
|
  M. Bourajjaj, A.-S. Armand, P. A. da Costa Martins, B. Weijts, R. van der Nagel, S. Heeneman, X. H. Wehrens, and L. J. De Windt NFATc2 Is a Necessary Mediator of Calcineurin-dependent Cardiac Hypertrophy and Heart Failure J. Biol. Chem., August 8, 2008; 283(32): 22295 - 22303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kaminuma, F. Kitamura, N. Kitamura, T. Hiroi, H. Miyoshi, A. Miyawaki, and S. Miyatake Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells J. Immunol., January 1, 2008; 180(1): 319 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dienz, S. M. Eaton, T. J. Krahl, S. Diehl, C. Charland, J. Dodge, S. L. Swain, R. C. Budd, L. Haynes, and M. Rincon Accumulation of NFAT mediates IL-2 expression in memory, but not naive, CD4+ T cells PNAS, April 24, 2007; 104(17): 7175 - 7180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dong, S. Kim, S. Hong, J. Das Gupta, K. Malathi, E. A. Klein, D. Ganem, J. L. DeRisi, S. A. Chow, and R. H. Silverman From the Cover: An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors PNAS, January 30, 2007; 104(5): 1655 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Hock and M. A. Brown Nuclear Factor of Activated T Cells 2 Transactivation in Mast Cells: A NOVEL ISOFORM-SPECIFIC TRANSACTIVATION DOMAIN CONFERS UNIQUE Fc{epsilon}RI RESPONSIVENESS J. Biol. Chem., July 11, 2003; 278(29): 26695 - 26703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van Rooij, P. A. Doevendans, C. C. de Theije, F. A. Babiker, J. D. Molkentin, and L. J. De Windt Requirement of Nuclear Factor of Activated T-cells in Calcineurin-mediated Cardiomyocyte Hypertrophy J. Biol. Chem., December 6, 2002; 277(50): 48617 - 48626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Amasaki, S. Adachi, Y. Ishida, M. Iwata, N. Arai, K.-i. Arai, and S. Miyatake A Constitutively Nuclear Form of NFATx Shows Efficient Transactivation Activity and Induces Differentiation of CD4+CD8+ T Cells J. Biol. Chem., July 5, 2002; 277(28): 25640 - 25648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshida, I. Ishikawa, Y. Ono, T. Imai, R. Suzuki, and O. Yoshie An Activation-Responsive Element in Single C Motif-1/Lymphotactin Promoter Is a Site of Constitutive and Inducible DNA-Protein Interactions Involving Nuclear Factor of Activated T Cell J. Immunol., September 15, 1999; 163(6): 3295 - 3303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chuvpilo, A. Avots, F. Berberich-Siebelt, J. Glockner, C. Fischer, A. Kerstan, C. Escher, I. Inashkina, F. Hlubek, E. Jankevics, et al. Multiple NF-ATc Isoforms with Individual Transcriptional Properties Are Synthesized in T Lymphocytes J. Immunol., June 15, 1999; 162(12): 7294 - 7301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, E. S. Masuda, L. Tsuruta, N. Arai, and K.-i. Arai Two Independent Calcineurin-Binding Regions in the N-Terminal Domain of Murine NF-ATx1 Recruit Calcineurin to Murine NF-ATx1 J. Immunol., April 15, 1999; 162(8): 4755 - 4761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Stevenson, M. F. Gomez, D. C. Hill-Eubanks, and M. T. Nelson NFAT4 Movement in Native Smooth Muscle. A ROLE FOR DIFFERENTIAL Ca2+ SIGNALING J. Biol. Chem., April 27, 2001; 276(18): 15018 - 15024. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
