| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Gene Expression in T Cells1
* Cytokine Project,
Department of Allergy and Immunology,
Calpain Project, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;
Subteam for Manipulation of Cell Fate, BioResource Center, Institute of Physical and Chemical Research, Tsukuba Institute, Ibaraki, Japan; and
¶ Laboratory for Cell Function and Dynamics, Advanced Technology Development Center, Brain Science Institute, Institute of Physical and Chemical Research, Saitama (RIKEN), Japan
The NFAT family transcription factors play crucial roles in immunological and other biological events; however, the functional differences among NFAT members have not been fully elucidated. This study investigated the relative contribution of NFATc2 and NFATc1 to the transactivation of cytokine genes in T cells. Ectopic expression of NFATc2 but not NFATc1, especially its short isoform, enhanced TNF-
synthesis in human T cells at the gene transcription level, whereas both NFATs augmented IL-2 expression. In addition, a reduction of the shortest NFATc1 isoform using RNA interference technology failed to suppress TNF- expression. The promoter/enhancer activity of the NFAT-binding site in the TNF- gene was up-regulated by NFATc2 but not by NFATc1, whereas both NFATs associated similarly with this region. A study of mRNA expression using NFATc2/NFATc1 chimeric molecules revealed that the enhancing activity of NFAT on the TNF- gene was lost by truncation of its C-terminal transactivation domain. In addition, this domain derived from NFATc2 behaved as a dominant negative against the NFAT site in TNF- promoter-dependent transcriptional activity in T cells. We conclude that the C-terminal transactivation domain in NFAT is crucial for TNF- gene expression in human T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants-in-aid from the Japan Health Science Foundation (to M.S.), the Uehara Memorial Foundation (to K.O.), the Naito Memorial Foundation (to K.O.), the Pharmacological Research Foundation (to K.O.), and the Research Foundation for Pharmaceutical Sciences (to K.O.).
2 Address correspondence and reprint requests to Dr. Osamu Kaminuma, Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. E-mail address: kaminuma{at}rinshoken.or.jp
3 Abbreviations used in this paper: DBD, DNA-binding domain; ChIP, chromatin immunoprecipitation; CRD, Ca2+ regulatory domain; EGFP, enhanced GFP; IRES, internal ribosomal entry site; RNAi, RNA interference; TAD, transactivation domain.
This article has been cited by other articles:
|
|
 |
|
  J. H. Maxeiner, R. Karwot, K. Sauer, P. Scholtes, I. Boross, M. Koslowski, O. Tureci, R. Wiewrodt, M. F. Neurath, H. A. Lehr, et al. A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes Cancer Res., April 1, 2009; 69(7): 3069 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
