Definition of the Roles for Iron and Essential Fatty Acids in Cell Cycle Progression of Normal Human T Lymphocytes

1993 ◽  
Vol 204 (2) ◽  
pp. 260-267 ◽  
Author(s):  
Naohiro Terada ◽  
Reuven Or ◽  
Agota Szepesi ◽  
Joseph J. Lucas ◽  
Erwin W. Gelfand
Keyword(s):  
Cell Cycle ◽  
Fatty Acids ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
Essential Fatty Acids ◽  
Cycle Progression ◽  
Human T Lymphocytes ◽  
Normal Human ◽  
Definition Of

scholarly journals Effects of Guanine Nucleotide Depletion on Cell Cycle Progression in Human T Lymphocytes

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2896-2904 ◽  
Author(s):  
Josée Laliberté ◽  
Ann Yee ◽  
Yue Xiong ◽  
Beverly S. Mitchell
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Guanine Nucleotides ◽  
Erythroid Cell ◽  
Guanine Nucleotide ◽  
Cycle Progression ◽  
Human T Lymphocytes

Depletion of guanine nucleotide pools after inhibition of inosine monophosphate dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cells in G1 and has been shown to induce the differentiation of cultured myeloid and erythroid cell lines, as well as chronic granulocytic leukemic cells after blast transformation. Inhibitors of IMPDH are also highly effective as immunosuppressive agents. The mechanism underlying these pleiotropic effects of depletion of guanine nucleotides is unknown. We have examined the effects of mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression of activated normal human T lymphocytes. MPA treatment resulted in the inhibition of pRb phosphorylation and cell entry into S phase. The expression of cyclin D3, a major component of the cyclin-dependent kinase (CDK) activity required for pRb phosphorylation, was completely abrogated by MPA treatment of T cells activated by interleukin-2 (IL-2) and leucoagglutinin (PHA-L), whereas the expression of cyclin D2, CDK6, and CDK4 was more mildly attenuated. The direct kinase activity of a complex immunoprecipitated with anti-CDK6 antibody was also inhibited. In addition, MPA prevented the IL-2–induced elimination of p27Kip1, a CDK inhibitor, and resulted in the retention of high levels of p27Kip1 in IL-2/PHA-L–treated T cells bound to CDK2. These results indicate that inhibition of the de novo synthesis of guanine nucleotides blocks the transition of normal peripheral blood T lymphocytes from G0 to S phase in early- to mid-G1 and that this cell cycle arrest results from inhibition of the induction of cyclin D/CDK6 kinase and the elimination of p27Kip1 inhibitory activity.

scholarly journals Soluble HLA-G Inhibits Cell Cycle Progression in Human Alloreactive T Lymphocytes

2006 ◽  
Vol 176 (3) ◽  
pp. 1331-1339 ◽  
Author(s):  
Rajia Bahri ◽  
Francois Hirsch ◽  
Adeline Josse ◽  
Nathalie Rouas-Freiss ◽  
Nicolas Bidere ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Soluble Hla

scholarly journals Sonic Hedgehog Promotes Cell Cycle Progression in Activated Peripheral CD4+ T Lymphocytes

2002 ◽  
Vol 169 (4) ◽  
pp. 1869-1875 ◽  
Author(s):  
Jacqueline A. Lowrey ◽  
Gareth A. Stewart ◽  
Susannah Lindey ◽  
Gerard F. Hoyne ◽  
Margaret J. Dallman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Lymphocytes ◽  
Sonic Hedgehog ◽  
Cell Cycle Progression ◽  
Cycle Progression

scholarly journals Cell cycle progression after cleavage failure

2004 ◽  
Vol 165 (5) ◽  
pp. 609-615 ◽  
Author(s):  
Yumi Uetake ◽  
Greenfield Sluder
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Human Fibroblasts ◽  
Human Cell Line ◽  
Cycle Progression ◽  
Binucleate Cells ◽  
Normal Human ◽  
Cleavage Failure

Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a “tetraploidy checkpoint” that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 μM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed through mitosis in >80% of the cases for the hTERT-RPE1 human cell line, primary human fibroblasts, and the REF52 cell line. These observations provide a functional demonstration that the tetraploidy checkpoint does not exist in normal mammalian somatic cells.

p21WAF1 is dynamically associated with JNK in human T-lymphocytes during cell cycle progression

1998 ◽  
Vol 111 (15) ◽  
pp. 2247-2255
Author(s):  
R. Patel ◽  
B. Bartosch ◽  
J.L. Blank
Keyword(s):  
Cell Cycle ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Human T Lymphocytes ◽  
Mitogen Activated Protein ◽  
Dependent Protein ◽  
Jnk Activation

We have examined the regulation of the c-Jun NH2-terminal kinase (JNK) subfamily of mitogen-activated protein kinases (MAPKs) in response to inhibition of DNA replication during the cell cycle of human T-lymphocytes. In this study, we demonstrate that JNK is rapidly activated following release of T-lymphocytes from G1/S-phase arrest and that this activation precedes resumption of DNA synthesis upon S-phase progression. We also show that activation of JNK correlates with dissociation of the cyclin-dependent protein kinase (CDK) inhibitor, p21WAF1, from JNK1. Since JNK1 isolated from T-lymphocytes by immunoprecipitation can be inhibited by recombinant p21WAF1 in vitro, these data suggest that JNK activation may be regulated in part by its dissociation from p21WAF1. The observation of a dynamic, physical association of native JNK1 and p21WAF1 in vivo has not previously been described and suggests a novel mechanism for JNK-mediated regulation of the cell cycle of human T-lymphocytes.

cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 998-1006 ◽  
Author(s):  
Thomas Grader-Beck ◽  
Andre A. F. L. van Puijenbroek ◽  
Lee M. Nadler ◽  
Vassiliki A. Boussiotis
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Phorbol Ester ◽  
Cell Cycle Progression ◽  
Cell Activation ◽  
Cytokine Production ◽  
Cycle Progression ◽  
Rap1 Activation

Abstract Cyclic adenosine monophosphate (cAMP) is a negative regulator of T-cell activation. However, the effects of cAMP on signaling pathways that regulate cytokine production and cell cycle progression remain unclear. Here, using primary human T lymphocytes in which endogenous cAMP was increased by the use of forskolin and 3-isobutyl-1-methylxanthine (IBMX), we show that increase of cAMP resulted in inhibition of T-cell receptor (TCR)/CD3 plus CD28–mediated T-cell activation and cytokine production and blockade of cell cycle progression at the G1 phase. Increase of cAMP inhibited Ras activation and phosphorylation of mitogen-induced extracellular kinase (MEK) downstream targets extracellular signal–related kinase 1/2 (ERK1/2) and phosphatidylinositol-3-kinase (PI3K) downstream target protein kinase B (PKB; c-Akt). These functional and biochemical events were secondary to the impaired activation of ZAP-70 and phosphorylation of LAT and did not occur when cells were stimulated with phorbol ester, which bypasses the TCR proximal signaling events and activates Ras. Increase of cAMP also inhibited activation of Rap1 mediated by TCR/CD3 plus CD28. Importantly, inhibition of Rap1 activation by cAMP was also observed when cells were stimulated with phorbol ester, although under these conditions Ras was activated and cells progressed into the cell cycle. Thus, TCR plus CD28–mediated activation of ERK1/2 and PKB, cytokine production, and cell cycle progression, all of which are inhibited by cAMP, require activation of Ras but not Rap1. These results indicate that signals that regulate cAMP levels after encounter of T cells by antigen will likely determine the functional fate toward clonal expansion or repression of primary T-cell responses.

4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes

2003 ◽  
Vol 223 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Hyeon-Woo Lee ◽  
Kyung-Ok Nam ◽  
Su K. Seo ◽  
Young H. Kim ◽  
Hyun Kang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
Cross Linking ◽  
Cycle Progression
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