Telomerase regulation at the crossroads of cell fate.
Telomeres are specialized structures at the ends of eukaryotic chromosomes and are crucial for genome stability, cell growth control and carcinogenesis. Normally, they protect chromosomes from end to end fusion, degradation and recombination. Telomerase is a ribonucleoprotein essential for maintenance of telomeres and it is active in germ cells, stem cells and approximately 90% of cancers but not in most normal somatic cells. Human telomerase catalytic protein subunit hTERT is crucial for telomerase activity. Although hTERT expression is sufficient to immortalize normal human cells in culture, spontaneous immortalization is extremely rare which suggests that its expression is under strong negative control. Characterization of the hTERT promoter has allowed for the analysis of potential mechanisms of hTERT expression and regulation. The hTERT promoter is very complex and contains a great number of canonical and non-canonical sequences that bind or potentially bind a variety of transcription factors. In this review we focus on the positive and negative regulators of hTERT transcription and their role in normal cell growth and immortalization.
Cukusić
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A
Laboratory of Experimental Cancerology, Department of Molecular Biology, Ruder Bosković Institute, Zagreb, Croatia.
Skrobot Vidacek
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N
Sopta
M
M
Rubelj
I
I
D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D016162:Genes, Wilms Tumor; D016158:Genes, p53; D015894:Genome, Human; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D025721:WT1 Proteins; D019098:Telomerase