ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells

Urbanowicz‐Kachnowicz, Iwona; Baghdassarian, Nathalie; Nakache, Corinne; Gracia, Delphine; Mekki, Yahia; Bryon, Paul‐André; Ffrench, Martine

doi:10.1002/(sici)1097-0215(19990702)82:1<98::aid-ijc17>3.0.co;2-a

Cited by 36 publications

(33 citation statements)

References 21 publications

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“…These data provide further evidence of the key role of Cks proteins in regulation of the metaphase/anaphase transition. 6,9,10 Furthermore, altered expression of these proteins has been associated with aggressiveness and proliferative state of hematological malignancies, 32 as in our fibrosarcoma development model system.…”

Section: Discussionmentioning

confidence: 94%

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Gascoyne¹,

Hixon²,

Gualberto³

et al. 2003

Cell Cycle

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Section: Discussionmentioning

confidence: 94%

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Gascoyne¹,

Hixon²,

Gualberto³

et al. 2003

Cell Cycle

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“…Cell fragmentation was carried out as previously described (46). Nuclear proteins were then cross-linked to DNA by incubation with 1% formaldehyde for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells

Chebel

Rouault

Urbanowicz

et al. 2009

Journal of Biological Chemistry

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Telomerase is essential for telomere maintenance, and its activation is thought to be a critical step in cellular immortalization and tumorigenesis. Human telomerase reverse transcriptase (hTERT) is a major component of telomerase activity. We show here that hTERT is expressed soon after lymphocyte activation and that its expression is inhibited by rapamycin, wortmannin, and FK506, which was the most potent inhibitor. These results suggest a potential role for the transcription factor nuclear factor of activated T cells (NFAT) in the regulation of hTERT expression. Five putative NFAT-binding sites were identified in the hTERT promoter. In luciferase assays, the hTERT promoter was activated by overexpressed NFAT1. Moreover, serial deletions revealed that the promoter activation was mainly due to a ؊40 NFAT1-binding site flanked by two SP1-binding sites. Mutation of the ؊40 NFAT-binding site caused a 53% reduction in the transcriptional activity of hTERT promoter. Simultaneous mutations of the ؊40 NFAT-responsive element together with one or both SP1-binding sites led to a more dramatic decrease in luciferase activity than single mutations, suggesting a functional synergy between NFAT1 and SP1 in hTERT transcriptional regulation. NFAT1 overexpression in MCF7 and Jurkat cell lines induced an increase in endogenous hTERT mRNA expression. Inversely, its down-regulation was induced by NFAT1 silencing. Furthermore, chromatin immunoprecipitation assay demonstrated that NFAT1 directly binds to two sites (؊40 and ؊775) in the endogenous hTERT promoter. Thus, we show for the first time the direct involvement of NFAT1 in the transcriptional regulation of hTERT.Telomeres are specialized structures located at the ends of linear mammalian chromosomes (1). The erosion of human telomeres at each cycle of cellular division is compensated for by de novo synthesis catalyzed by human telomerase reverse transcriptase (hTERT), 3 the catalytic subunit of a ribonucleoprotein complex called telomerase (2). Telomerase maintains telomeres by protecting them from exonucleases and ligases and by preventing illegitimate recombination (3). However, hTERT is also implicated in cell immortalization and tumorigenesis (4) through its telomere-lengthening activity, as well as by a mechanism independent of telomere length (5).Most normal human somatic tissues do not express hTERT, but germinal cells, several types of normally activated or proliferating cells, and tumor cells do (6 -13). In particular, lymphocytes exhibit telomerase activity in response to stimulation (14). Regulation of telomerase expression in these cells is likely to occur in the G 1 phase of the cell cycle as telomerase is inhibited by rapamycin, a compound that affects the mammalian target of rapamycin (mTOR) but is not inhibited by aphidicolin or hydroxyurea, substances that inhibit DNA synthesis (14 -16). Phosphorylation of hTERT and the resulting effects on its nuclear translocation and telomerase activity have been well described (17, 18). These post-translational modificati...

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“…Cell fractionation was performed with freshly harvested cells as previously described 52 in order to recover proteins from the nuclear and cytoplasmic fractions. The detection of nuclear Lamin A was an indicator of the quality of cell fractionation.…”

Section: Notementioning

confidence: 99%

S-phase lengthening induced by p16^INK4aoverexpression in malignant cells with wild-type pRb and p53

et al. 2010

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ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells

Cited by 36 publications

References 21 publications

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells

S-phase lengthening induced by p16^INK4aoverexpression in malignant cells with wild-type pRb and p53

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ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells

Cited by 36 publications

References 21 publications

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells

S-phase lengthening induced by p16INK4aoverexpression in malignant cells with wild-type pRb and p53

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S-phase lengthening induced by p16^INK4aoverexpression in malignant cells with wild-type pRb and p53