Telomerase reverse transcriptase hTERT

Dasi F, Lledo S, Garcia-Granero E, RipoU R, Marugan M, Tormo M, et al. Real-time quantification in plasma of human telomerase reverse transcriptase (hTERT) mRNA a simple blood test to monitor disease in cancer patients. Lab Invest 2001 81 767-9. 

Trott, D.A., Newbold, R.F., and Nabholz, M. (2003). A chromosome 3-encoded repressor of the human telomerase reverse transcriptase (hTERT) gene controls the state ofhTERT chromatin. Gancer Res. 63, 689-695. 

Figure 10.11 Schematic diagram of (a) formation of small interfering RNA (siRNA) loaded polyethylene glycol (PEG)- carboxymethyl chitosan (CMCS)/CaP hybrid anionic nanoparticles (NPPEG-CMCS/CaP/siRNA). (b) NPPEG-CMCS/CaP/siRNA for systemic delivery of human telomerase reverse transcriptase (hTERT) siRNA in anticancer therapy.

Beyond the Hayflick limit, cells that have escaped senescence and/or crisis must progress beyond mortality stage 2 (Figure 26.1). Recent studies have shown that human telomerase reverse transcriptase cDNA (hTERT) in combination with viral oncogenes also has the potential to immortalize human airway epithelial cells [15, 78-82], However, even though hTERT alone will cause enhanced growth potential of a cell line, with the exception of one study [81],... 

Kyo S, Takakura M, Taira T, Kanaya T, Itoh H, et al. 2000. Spl cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 28 669-77... 

As often happens in these days of the human genome project, the human version hTERT) was found shortly thereafter [16, 17]. It was expressed in a variety of transformed cells but not detectable in primary cultures of human somatic cells, already giving a simple answer as to why telomerase activity was deficient in somatic cells. Thus, over a short time span, we went from having no telomerase protein to a whole family of TERTs (Telomerase Reverse Transcriptases). 

Retroviral-mediated transduction of hTERT (human telomerase reverse transcriptase) in human dermal microvascular endothelial cells (EC) (HDMEC) results in cell lines that form microvascular structures upon subcutaneous implantation in severe combined immunodeficiency mice (SCID) mice. Anti-human type IV collagen basement membrane immii-noreactivity and visualization of enhanced green fluorescent protein (eGFP)-labeled microvessels confirmed the human origin of these vessels. Primary HDMEC-derived vessel density decreased with time, while telomerized HDMEC maintained durable vessels six... 

The telomerase holoenzyme core consists of a catalytic subunit, the reverse transcriptase protein hTERT (1-3), and an RNA template subunit, hTR (4), which are essential for telomerase activity (5). Otherproteins (6,7) and kinases (8-11) are... 

Telomerase activity can also be inhibited by the direct binding of small non-nucleosidic synthetic compounds to the hTERT reverse transcriptase component of telomerase. Schnapp and coworkers have recently reported the first mixed-type noncompetitive (70) catalytic telomerase inhibitor, (2-((E)-3-naphtalen-2-yl-but-2-enoylamino)-benzoic acid) (BIBR1532), which causes telomere shortening and senescence characteristics in various types of cancer cells in vitro and in vivo in mouse xenograft models at nanomolar concentrations (71). 

Some cells that lack telomerase activity, on the other hand, still have a high level of hTERT transcription. In these cases, regulation at the level of alternative splicing leads to skipping of exons that encode reverse transcriptase function, so any translation product would not give an active enzyme [47]. 

---