|
|
 Previous Article | Table of Contents | Next Article 
Control of cell cycle progression in human natural killer cells through
redox regulation of expression and phosphorylation of retinoblastoma gene
product protein
A Yamauchi and ET Bloom
Center for Biologics Evaluation and Research, Food and Drug Administration,
Bethesda, MD 20892, USA.
Using thiol deprivation, we have previously shown that the response of
natural killer (NK) cells to interleukin-2 (IL-2) is subject to redox
regulation downstream of IL-2 binding and internalization. We have now used
the IL-2-dependent cell line, NK3.3 to study redox regulation of NK cells
further, and found that NK3.3 cells neither incorporated [3H]- thymidine
nor completed the G1-S phase transition in medium lacking the thiol-related
compounds, L-cystine, and glutathione, despite the presence of sufficient
IL-2. Thiol deprivation did not alter the induction of DNA interferon-gamma
activated sequence (GAS)-binding activity in response to IL-2. However, the
retinoblastoma gene product (RB), a cyclin-dependent kinase (CDK)
substrate, was phosphorylated within 24 hours after IL-2 stimulation in
standard medium, but its expression and phosphorylation were reduced in
thiol-depleted medium in both NK3.3 cells and freshly isolated NK cells.
These reductions were not associated with an increased level of p27Kip1, an
inhibitor of CDKs CDK6/2 in association with G1 cyclins. Reducing agents,
N- acetylcysteine, reduced glutathione or 2-ME restored both RB
phosphorylation and DNA synthesis in thiol-deprived NK3.3 cells. The in
vitro kinase activities of CDK6 and CDK2 were prematurely increased by
thiol deprivation. This enhancement was associated with CDK
hyperphosphorylation and prolonged phosphorylation, and could be observed
before and beyond IL-2 stimulation. The data suggest the possibility that
the premature and prolonged enhancement of CDK activity in thiol-deprived
NK cells is associated with, and therefore may contribute to, the reduced
expression and phosphorylation of RB, and the associated cell cycle arrest.
Volume 89,
Issue 11,
pp. 4092-4099,
06/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
O Arroyo-Helguera, E Rojas, G Delgado, and C Aceves
Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects
Endocr. Relat. Cancer,
December 1, 2008;
15(4):
1003 - 1011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Ying, A. B. Hofseth, D. D. Browning, M. Nagarkatti, P. S. Nagarkatti, and L. J. Hofseth
Nitric Oxide Inactivates the Retinoblastoma Pathway in Chronic Inflammation
Cancer Res.,
October 1, 2007;
67(19):
9286 - 9293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Menon, E. H. Sarsour, A. L. Kalen, S. Venkataraman, M. J. Hitchler, F. E. Domann, L. W. Oberley, and P. C. Goswami
Superoxide Signaling Mediates N-acetyl-L-cysteine-Induced G1 Arrest: Regulatory Role of Cyclin D1 and Manganese Superoxide Dismutase
Cancer Res.,
July 1, 2007;
67(13):
6392 - 6399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Martirosyan, S. Leonard, X. Shi, B. Griffith, P. Gannett, and J. Strobl
Actions of a Histone Deacetylase Inhibitor NSC3852 (5-Nitroso-8-quinolinol) Link Reactive Oxygen Species to Cell Differentiation and Apoptosis in MCF-7 Human Mammary Tumor Cells
J. Pharmacol. Exp. Ther.,
May 1, 2006;
317(2):
546 - 552.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hadzic, L. Li, N. Cheng, S. A. Walsh, D. R. Spitz, and C. M. Knudson
The Role of Low Molecular Weight Thiols in T Lymphocyte Proliferation and IL-2 Secretion
J. Immunol.,
December 15, 2005;
175(12):
7965 - 7972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Menon, E. H. Sarsour, D. R. Spitz, R. Higashikubo, M. Sturm, H. Zhang, and P. C. Goswami
Redox Regulation of the G1 to S Phase Transition in the Mouse Embryo Fibroblast Cell Cycle
Cancer Res.,
May 1, 2003;
63(9):
2109 - 2117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tsuyuki, J. A. Horvath-Arcidiacono, and E. T. Bloom
Effect of Redox Modulation on Xenogeneic Target Cells: The Combination of Nitric Oxide and Thiol Deprivation Protects Porcine Endothelial Cells from Lysis by IL-2-Activated Human NK Cells
J. Immunol.,
March 15, 2001;
166(6):
4106 - 4114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Furuke, P. R. Burd, J. A. Horvath-Arcidiacono, K. Hori, H. Mostowski, and E. T. Bloom
Human NK Cells Express Endothelial Nitric Oxide Synthase, and Nitric Oxide Protects Them from Activation-Induced Cell Death by Regulating Expression of TNF-{alpha}
J. Immunol.,
August 1, 1999;
163(3):
1473 - 1480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Furuke, M. Shiraishi, H. S. Mostowski, and E. T. Bloom
Fas Ligand Induction in Human NK Cells Is Regulated by Redox Through a Calcineurin-Nuclear Factors of Activated T Cell-Dependent Pathway
J. Immunol.,
February 15, 1999;
162(4):
1988 - 1993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
