The Regulation of Telomerase in Oncogenesis
- Авторы: Skvortzov DA1, Rubzova MP1, Zvereva ME1, Kiselev FL1, Donzova OA1
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Учреждения:
- Выпуск: Том 1, № 1 (2009)
- Страницы: 51-67
- Раздел: Статьи
- Дата подачи: 17.01.2020
- Дата публикации: 15.06.2009
- URL: https://actanaturae.ru/2075-8251/article/view/10812
- DOI: https://doi.org/10.32607/20758251-2009-1-1-51-67
- ID: 10812
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Аннотация
Telomerase is a complex ribonucleoprotein that completes the telomeres' ends in eukaryotic cells which shorten due to DnA underreplication. the core enzyme consists of a protein catalytic subunit—telomerase reverse transcriptase (tert)—and telomeric rnA (telomerase rnA (tr)); a small region of this rnA serves as a template for the telomeric repeats synthesis. Apart from rare exceptions, telomerase is not active in the somatic cells and tissues of the human body. However, the activation of telomerase activity in cancer cells was shown for certain in 80–90 % of cases. understanding the mechanism of telomerase functioning and the mechanisms of its regulation could be used in oncodiagnostics. telomerase itself and its regulators could be important targets for anticancer therapy. the activity of telomerase in a cell is affected by proteins with multiple functions, and this influence is not necessarily specific. there are also cases when telomerase regulators act together or when several regulators are organised in the cascade. the aim of this review is to generalize and systemize data about the regulation of telomerase in ontogenesis. Key words: telomerase, telomerase reverse transcriptase, telomerase rnA, regulation, cancer. Abbreviations: 5azadc (5-aza-2'-deoxicitidine), AV (adenoviruses), HBV (Hepatitis B Virus) HIV (Human Immunodeficiency Virus), HPV (Human papillomavirus), eBV (epstein–Barr Virus), np (nucleotide pair), OB-motive (oligonecleotide/oligosaccharide binding motive), rt (reverse transcription), Pcr (polymerase chain reacion), rnAse (ribonuclease), tert (telomerase reverse transcriptase), htert (human tert), mtert (mouse tert), Dn-htert (dominantnegative mutated htert), erβ (estrogen β receptor), HtLV-I (Human t-lymphotropic virus), tr (telomerase rnA), trAP (telomeric repeat Amplification Protocol), PHA (phytohemagglutinin), Hre (Hypoxia response element), neS (nuclear export signal).
Полный текст
1961 Hayflick and Moorhead showed that a so-subunits of reverse transcriptase and two rnA molecules matic cell culture has a limited life span [1]. In 1973 [6]. In human telomerase, p23/p90-shaperone, which is re-Olovnikov suggested that shortening the chro-sponsible for the complex assembling/configuration, binds mosomal ends (telomeres) determines the potential number 14-3-3, which is responsible for nuclear localization, and of cell divisions. [2]. telomeres protect the cellular genome tP1 with an unknown function. Proteins hGAr1, Dyskerin/ from degradation; they participate in the chromosomal pair-nAP57, hnHP2, and c1/c2, which are responsible for the ing during meiosis and in the gene expression regulation in stability, maturation, and localisation of rnA, bind to the the telomeres region [3]. In immortal cells that can divide htr; La and hStau, which are supposedly responsible for infinitely, this should be the mechanism for compensating the binding to telomeres; L22, which acts in processing and the chromosomal shortening. In 1975 Blackburn and Greider nuclear localisation; and hnOP10, A1/uP1, and tP1 with an discovered the enzyme telomerase that elongates chromo-unknown function [7]; tcAB1, which is responsible for the somes [4]. localisation of htr in cajal bodies and binding with telom telomerase is a ribonucleoprotein complex that consists ers [8]. the enzymatic activity of human telomerase in the of components that are absolutely required for its activity: rabbit reticulocytes lysate is detected by adding htr and the rnA molecule and telomerase reverse transcriptase htert [9, 10]. note that telomerase functioning in vivo is tert [5]; also, optionally several telomerase-associated pro-not always consistent with the telomerase activity that was teins could be included in the telomerase complex. tr is also measured in vitro. For example, adding the Hemagglutinin a template for tert when telomerase elongates telomeres. epitope to the c-end of htert stops telomere alongation telomerase exists in human cells as dimers and contains two but does not suppress telomerase activity [11].×
Об авторах
D A Skvortzov
M P Rubzova
M E Zvereva
F L Kiselev
O A Donzova
Email: dontsova@genebee.msu.su
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