A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter

2001 ◽  
Author(s):  
Tadashi Komata ◽  
Shoji Koga ◽  
Satoshi Hirohata ◽  
Masahiro Takakura ◽  
Isabelle Germano ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Gene Promoter ◽  
Telomerase Reverse Transcriptase ◽  
Reverse Transcriptase Gene ◽  
Human Telomerase Reverse Transcriptase ◽  
Novel Treatment ◽  
Fadd Gene ◽  
Human Telomerase

Human Telomerase Reverse Transcriptase Gene Promoter Mutation in Serum of Patients with Hepatocellular Carcinoma

Oncology ◽  
2020 ◽  
Vol 98 (5) ◽  
pp. 311-317
Author(s):  
Soichiro Ako ◽  
Kazuhiro Nouso ◽  
Hideaki Kinugasa ◽  
Hiroshi Matsushita ◽  
Hiroyuki Terasawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Reverse Transcriptase ◽  
Gene Promoter ◽  
Telomerase Reverse Transcriptase ◽  
Reverse Transcriptase Gene ◽  
Promoter Mutation ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

scholarly journals Identification of human TERT elements necessary for telomerase recruitment to telomeres

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jens C Schmidt ◽  
Andrew B Dalby ◽  
Thomas R Cech
Keyword(s):  
Dna Sequences ◽  
Repetitive Dna Sequences ◽  
Telomerase Reverse Transcriptase ◽  
Human Chromosomes ◽  
Human Telomerase Reverse Transcriptase ◽  
Interaction Interface ◽  
Ob Fold ◽  
Human Telomerase

Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease.

scholarly journals Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7176 ◽  
Author(s):  
Haley D. M. Wyatt ◽  
Allison R. Tsang ◽  
Deirdre A. Lobb ◽  
Tara L. Beattie
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

scholarly journals Functional Multimerization of the Human Telomerase Reverse Transcriptase

2001 ◽  
Vol 21 (18) ◽  
pp. 6151-6160 ◽  
Author(s):  
Tara L. Beattie ◽  
Wen Zhou ◽  
Murray O. Robinson ◽  
Lea Harrington
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Human Telomerase Reverse Transcriptase ◽  
Catalytic Core ◽  
Cell Extracts ◽  
Human Telomerase

ABSTRACT The telomerase enzyme exists as a large complex (∼1,000 kDa) in mammals and at minimum is composed of the telomerase RNA and the catalytic subunit telomerase reverse transcriptase (TERT). In Saccharomyces cerevisiae, telomerase appears to function as an interdependent dimer or multimer in vivo (J. Prescott and E. H. Blackburn, Genes Dev. 11:2790–2800, 1997). However, the requirements for multimerization are not known, and it remained unclear whether telomerase exists as a multimer in other organisms. We show here that human TERT (hTERT) forms a functional multimer in a rabbit reticulocyte lysate reconstitution assay and in human cell extracts. Two separate, catalytically inactive TERT proteins can complement each other in trans to reconstitute catalytic activity. This complementation requires the amino terminus of one hTERT and the reverse transcriptase and C-terminal domains of the second hTERT. The telomerase RNA must associate with only the latter hTERT for reconstitution of telomerase activity to occur. Multimerization of telomerase also facilitates the recognition and elongation of substrates in vitro and in vivo. These data suggest that the catalytic core of human telomerase may exist as a functionally cooperative dimer or multimer in vivo.

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