scholarly journals RNA Conformation in Catalytically Active Human Telomerase

2010 ◽  
Vol 132 (9) ◽  
pp. 2852-2853 ◽  
Author(s):  
Justin A. Yeoman ◽  
Angel Orte ◽  
Beth Ashbridge ◽  
David Klenerman ◽  
Shankar Balasubramanian
Keyword(s):  
Rna Conformation ◽  
Catalytically Active ◽  
Human Telomerase

Protein Composition of Catalytically Active Human Telomerase from Immortal Cells

Science ◽  
2007 ◽  
Vol 315 (5820) ◽  
pp. 1850-1853 ◽  
Author(s):  
S. B. Cohen ◽  
M. E. Graham ◽  
G. O. Lovrecz ◽  
N. Bache ◽  
P. J. Robinson ◽  
...  
Keyword(s):  
Protein Composition ◽  
Catalytically Active ◽  
Immortal Cells ◽  
Human Telomerase

scholarly journals C-Terminal Regions of the Human Telomerase Catalytic Subunit Essential for In Vivo Enzyme Activity

2002 ◽  
Vol 22 (17) ◽  
pp. 6234-6246 ◽  
Author(s):  
Soma S. R. Banik ◽  
Chuanhai Guo ◽  
Allyson C. Smith ◽  
Seth S. Margolis ◽  
D. Ashley Richardson ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Human Cancer ◽  
Catalytic Subunit ◽  
Human Cancer Cells ◽  
C Terminus ◽  
Catalytically Active ◽  
Higher Eukaryotes ◽  
Human Telomerase

ABSTRACT Most human cancer cells are thought to acquire the ability to divide beyond the capacity of normal somatic cells through illegitimately activating the gene hTERT, which encodes the catalytic subunit of telomerase. While telomerase reverse transcriptase (TERT) is conserved in most eukaryotes, mounting evidence suggests that the C terminus of the human protein may have functions unique to higher eukaryotes. To search for domains responsible for such functions, we assayed a panel of tandem substitution mutations encompassing this region of human TERT for in vitro and in vivo functionality. We found four clusters of mutations that inactivated the biochemical and biological functions of telomerase, separated by mutations that had little or no effect on enzyme activity. We also identified a region where mutations generate catalytically active but biologically inert proteins. This C-terminal region that dissociates activities of telomerase (C-DAT) does not appear to be involved in nuclear localization or protein multimerization. Instead, it appears that the C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. Intriguingly, all of the described regions reside in a portion of TERT that is dispensable for cellular viability in yeast, arguing for a divergent role of the C terminus in higher eukaryotes.

Hsp90-binding immunophilin FKBP52 modulates telomerase activity by promoting the cytoplasmic retrotransport of hTERT

2016 ◽  
Vol 473 (20) ◽  
pp. 3517-3532 ◽  
Author(s):  
Yu Young Jeong ◽  
Joonyoung Her ◽  
Sue-Young Oh ◽  
In Kwon Chung
Keyword(s):  
Nuclear Translocation ◽  
Nuclear Transport ◽  
Heat Shock Protein 90 ◽  
Telomerase Activity ◽  
Human Telomerase Reverse Transcriptase ◽  
Peptidyl Prolyl Isomerase ◽  
Fk506 Binding Protein ◽  
Catalytically Active ◽  
Tetratricopeptide Repeat Domain ◽  
Human Telomerase

Telomerase is a unique ribonucleoprotein enzyme that is required for continued cell proliferation. To generate catalytically active telomerase, human telomerase reverse transcriptase (hTERT) must translocate to the nucleus and assemble with the RNA component of telomerase. The molecular chaperones heat shock protein 90 (Hsp90) and p23 maintain hTERT in a conformation that enables nuclear translocation. However, the regulatory role of chaperones in nuclear transport of hTERT remains unclear. In this work, we demonstrate that immunophilin FK506-binding protein (FKBP)52 linked the hTERT–Hsp90 complex to the dynein–dynactin motor, thereby promoting the transport of hTERT to the nucleus along microtubules. FKBP52 interacted with the hTERT–Hsp90 complex through binding of the tetratricopeptide repeat domain to Hsp90 and binding of the dynamitin (Dyt) component of the dynein-associated dynactin complex to the peptidyl prolyl isomerase domain. The depletion of FKBP52 inhibited nuclear transport of hTERT, resulting in cytoplasmic accumulation. Cytoplasmic hTERT was rapidly degraded through ubiquitin (Ub)-dependent proteolysis, thereby abrogating telomerase activity. In addition, overexpression of dynamitin, which is known to dissociate the dynein–dynactin motor from its cargoes, reduced telomerase activity. Collectively, these results provide a molecular mechanism by which FKBP52 modulates telomerase activity by promoting dynein–dynactin-dependent nuclear import of hTERT.

scholarly journals An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1

Cell ◽  
2018 ◽  
Vol 174 (1) ◽  
pp. 218-230.e13 ◽  
Author(s):  
Lu Chen ◽  
Caitlin M. Roake ◽  
Adam Freund ◽  
Pedro J. Batista ◽  
Siqi Tian ◽  
...  
Keyword(s):  
Rna Conformation ◽  
Human Telomerase

Growth of Catalytically Active Nanostructures in the Nonequilibrium Epitaxy Regime

2015 ◽  
Vol 60 (6) ◽  
pp. 546-552
Author(s):  
V.M. Gorshkov ◽  
◽  
V.V. Kuzmenko
Keyword(s):  
Catalytically Active
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