Abstract
The telomerase ribonucleoprotein complex has a pivotal role in regulating the proliferation and senescence of normal somatic cells as well as cancer cells. This complex is comprised mainly of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) and other associated proteins that function to elongate telomeres localized at the end of the chromosomes. While reactivation of telomerase is a major hallmark of most cancers, together with the synergistic activation of other oncogenic signals, deficiency in telomerase and telomeric proteins might lead to aging and senescence-associated disorders. Therefore, it is critically important to understand the canonical as well as non-canonical functions of telomerase through TERT to develop a therapeutic strategy against telomerase-related diseases. In this review, we shed light on the regulation and function of telomerase, and current therapeutic strategies against telomerase in cancer and age-related diseases.
Highlights
Telomeres are short, non-protein coding hexanucleotide repeats of TTAGGG which localize at the end of the chromosomes in association with protective proteins collectively termed shelterin
Since the dominant regulation mechanism of telomeres is dependent on the telomerase activity, we focus on telomerase in this review
Other supporting studies have shown that over-expression of human TERT (hTERT) in mammary epithelial cells reduced their dependence on external mitogens through regulation of proliferation genes [78], while the inhibition of telomerase induced apoptosis in ovarian cancer cells [79]
Summary
Non-protein coding hexanucleotide repeats of TTAGGG which localize at the end of the chromosomes in association with protective proteins collectively termed shelterin. Telomeres shorten after each cell division [2], because the gap between the final RNA primer and end of the chromosome cannot be completed in the strand where replication is performed by Okazaki fragments, and 3’ overhangs occur [3]. This progressive telomere shortening following each cycle of cell division is commonly known as the “end replication problem” and when telomeres become critically short, cells undergo a senescent state termed “Hayflick limit”. Of telomerase occurs in the Cajal bodies and the trafficking of telomerase to telomeres are mediated by TCAB1 and TPP1 proteins [10]
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