| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Division of Basic Sciences, Laboratory of Experimental Immunology, National Cancer Institute, and
Intramural Research Support Program, Science Applications International Corp. Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
The pore-forming protein perforin is preferentially expressed in NK
and cytotoxic T cells. To investigate the molecular regulation of human
perforin gene transcription, the activity of the human perforin
promoter was analyzed in human NK and T cell lines using various
promoter fragments linked to a luciferase reporter gene. A core
promoter was identified within 55 bp upstream of the transcription
start site. This promoter region contains a guanine/cytosine box
and has basal activity in YT, Kit225-k6, and Jurkat cells. A strong
enhancer activity was identified between positions -1136 and -1076, a
region that includes a STAT-like element. This enhancer region was
active in YT cells, which have constitutive perforin expression and
activated STAT3 protein, but not in Kit225-k6 or Jurkat cells, which do
not have constitutive perforin expression. Mutation of the STAT binding
site resulted in a dramatic down-regulation of promoter activity.
Electrophoretic mobility shift assays, using a probe containing the
STAT element of the perforin promoter, indicated that this element can
bind STAT3 from YT cells. Moreover, the STAT element was shown to bind
STAT5a/b induced by IL-2 as well as STAT1
induced by IL-6 in human
NK cells. Together, these results suggest that STAT proteins play a key
role in perforin gene transcription and provide a model by which
cytokines can regulate perforin gene expression.
This article has been cited by other articles:
|
|
 |
|
  K. J. Marr, G. J. Jones, C. Zheng, S. M. Huston, M. Timm-McCann, A. Islam, B. M. Berenger, L. L. Ma, J. C. D. Wiseman, and C. H. Mody Cryptococcus neoformans Directly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity Infect. Immun., June 1, 2009; 77(6): 2436 - 2446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Thedrez, C. Harly, A. Morice, S. Salot, M. Bonneville, and E. Scotet IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human V{gamma}9V{delta}2 T Cells for Adoptive Immunotherapy J. Immunol., March 15, 2009; 182(6): 3423 - 3431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gorjao, S. M. Hirabara, T. M. de Lima, M. F. Cury-Boaventura, and R. Curi Regulation of interleukin-2 signaling by fatty acids in human lymphocytes J. Lipid Res., September 1, 2007; 48(9): 2009 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Casey and M. F. Mescher IL-21 Promotes Differentiation of Naive CD8 T Cells to a Unique Effector Phenotype J. Immunol., June 15, 2007; 178(12): 7640 - 7648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. White, S. Krishnan, N. Strbo, H. Liu, M. A. Kolber, M. G. Lichtenheld, R. N. Pahwa, and S. Pahwa Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV) Blood, May 1, 2007; 109(9): 3873 - 3880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Janas, P. Groves, N. Kienzle, and A. Kelso IL-2 Regulates Perforin and Granzyme Gene Expression in CD8+ T Cells Independently of Its Effects on Survival and Proliferation J. Immunol., December 15, 2005; 175(12): 8003 - 8010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Shacklett, C. A. Cox, M. F. Quigley, C. Kreis, N. H. Stollman, M. A. Jacobson, J. Andersson, J. K. Sandberg, and D. F. Nixon Abundant Expression of Granzyme A, but Not Perforin, in Granules of CD8+ T Cells in GALT: Implications for Immune Control of HIV-1 Infection J. Immunol., July 1, 2004; 173(1): 641 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Lu, A. Wu, D. Ray, C. Deng, J. Attwood, S. Hanash, M. Pipkin, M. Lichtenheld, and B. Richardson DNA Methylation and Chromatin Structure Regulate T Cell Perforin Gene Expression J. Immunol., May 15, 2003; 170(10): 5124 - 5132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhou and G. G. Meadows Alcohol Consumption Decreases IL-2-Induced NF-{kappa}B Activity in Enriched NK Cells from C57BL/6 Mice Toxicol. Sci., May 1, 2003; 73(1): 72 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Wulffraat, G. T. Rijkers, E. Elst, R. Brooimans, and W. Kuis Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation Rheumatology, February 1, 2003; 42(2): 375 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, J. Zhang, M. G. Lichtenheld, and G. G. Meadows A Role for NF-{kappa}B Activation in Perforin Expression of NK Cells Upon IL-2 Receptor Signaling J. Immunol., August 1, 2002; 169(3): 1319 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Burnett and J. S. Hunt Nitric Oxide Synthase-2 and Expression of Perforin in Uterine NK Cells J. Immunol., May 15, 2000; 164(10): 5245 - 5250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, I. Scordi, M. J. Smyth, and M. G. Lichtenheld Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers J. Exp. Med., November 1, 1999; 190(9): 1297 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Ehret, P. Reichenbach, U. Schindler, C. M. Horvath, S. Fritz, M. Nabholz, and P. Bucher DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES J. Biol. Chem., February 23, 2001; 276(9): 6675 - 6688. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
