[Telomerase, elixir of life for human cells?].

Telomeres are specialized structures at the end of eukaryotic chromosomes that in vertebrates constain hundreds to thousands of tandem repeats of the sequence TTAGGG. In most human somatic cells, telomeres shorten with each cell division, eventually triggering an irreversible arrest of proliferation called cellular senescence. These observations have led to a model in which telomere length reflects the mitotic history of somatic cells.

Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions.

After antigenic challenge, naive T lymphocytes enter a program of proliferation and differentiation during the course of which they acquire effector functions and may ultimately become memory cells. In humans, the pathways of effector and memory T-cell differentiation remain poorly defined. Here we describe the properties of 2 CD8+ T-lymphocyte subsets, RA+CCR7-27+28+ and RA+CCR7-27+28-, in human peripheral blood.

A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed.

Telomeres protect the eukaryotic chromosome ends from degradation and fusion. They are maintained by the ribonucleoprotein telomerase, the core of which is composed of a reverse transcriptase (TERT) and a RNA subunit. In the yeast Saccharomyces cerevisiae, a third critical telomerase subunit, the Ever Shorter Telomeres 1 (EST1) gene product, recruits or activates telomerase at the 3' end of telomeres.

A chromosome 3-encoded repressor of the human telomerase reverse transcriptase (hTERT) gene controls the state of hTERT chromatin.

Telomerase is crucial for human carcinogenesis. The limiting component of telomerase activity is telomerase reverse transcriptase (hTERT), undetectable in differentiated somatic cells but present in most tumor cells. There is evidence that hTERT transcription is shut down by a repressor in normal cells, but the mechanisms that turn on or maintain expression in tumor cells are not understood.

Induction of interleukin-2 receptor alpha (IL-2Ralpha) expression by interleukin-2: important role of the interleukin-2 receptor beta chain region between the two Stat5 docking sites.

The interleukin-2 receptor alpha (IL-2Ralpha) forms, together with IL-2Rbeta and gammac chains, a high affinity IL-2 receptor that is important for IL-2 responsiveness and normal T cell function. Expression of the IL-2Ralpha gene by T cells is regulated mainly at the transcription level which is transiently activated by antigen and upregulated and then prolonged by stimulation with IL-2. The effect of IL-2 on the IL-2Ralpha gene depends on the activation of the transcription factor Stat5, which acts on an IL-2- responsive enhancer that consists of two Stat5 and an Elf1 binding site.

Detection of promoter activity by flow cytometric analysis of GFP reporter expression.

Low efficiency of transfection is often the limiting factor for acquiring conclusive data in reporter assays. It is especially difficult to efficiently transfect and characterize promoters in primary human cells. To overcome this problem we have developed a system in which reporter gene expression is quantified by flow cytometry.

Regulation of the human telomerase reverse transcriptase gene.

Most somatic human cells lack telomerase activity because they do not express the telomerase reverse transcriptase (hTERT) gene. Conversely, most cancer cells express hTERT and are telomerase positive. For most tumors it is not clear whether hTERT expression is due to their origin from telomerase positive stem cells or to reactivation of the gene during tumorigenesis.