N-terminal domains of the human telomerase catalytic subunit required for enzyme activity in vivo

Molecular and Cellular Biology
Blaine N ArmbrusterC M Counter

Abstract

Most tumor cells depend upon activation of the ribonucleoprotein enzyme telomerase for telomere maintenance and continual proliferation. The catalytic activity of this enzyme can be reconstituted in vitro with the RNA (hTR) and catalytic (hTERT) subunits. However, catalytic activity alone is insufficient for the full in vivo function of the enzyme. In addition, the enzyme must localize to the nucleus, recognize chromosome ends, and orchestrate telomere elongation in a highly regulated fashion. To identify domains of hTERT involved in these biological functions, we introduced a panel of 90 N-terminal hTERT substitution mutants into telomerase-negative cells and assayed the resulting cells for catalytic activity and, as a marker of in vivo function, for cellular proliferation. We found four domains to be essential for in vitro and in vivo enzyme activity, two of which were required for hTR binding. These domains map to regions defined by sequence alignments and mutational analysis in yeast, indicating that the N terminus has also been functionally conserved throughout evolution. Additionally, we discovered a novel domain, DAT, that "dissociates activities of telomerase," where mutations left the enzyme catalytically active, but w...Continue Reading

References

May 31, 1990·Nature·C B HarleyC W Greider
Aug 30, 1990·Nature·N D HastieR C Allshire
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·I A WilsonS Brenner
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Sep 1, 1995·Science·J FengJ Yu
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·C M CounterC B Harley
Jun 1, 1996·Molecular and Cellular Biology·S E HoltJ W Shay
Apr 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S E HoltJ W Shay
Apr 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J W Shay, S Bacchetti
Nov 14, 1997·Genes & Development·J Prescott, E H Blackburn
Feb 12, 1998·Genes & Development·L HarringtonM O Robinson
Mar 20, 1998·Cell·T M Nakamura, T R Cech
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T M BryanT R Cech
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M Sedivy
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·C M CounterR A Weinberg
Jan 28, 1999·Biochemical and Biophysical Research Communications·M M OuelletteJ W Shay
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·J ZhuE H Blackburn
May 25, 1999·Cell·J D GriffithT de Lange
Aug 10, 1999·Nature·W C HahnR A Weinberg
Sep 29, 1999·Genes & Development·X ZhangM O Robinson
Sep 30, 1999·Nature Medicine·W C HahnR A Weinberg
Oct 3, 1999·Science·S K Evans, V Lundblad
Dec 23, 1999·The Journal of Biological Chemistry·F Bachand, C Autexier
Jan 11, 2000·Molecular and Cellular Biology·A Adams MartinC Holm
Feb 25, 2000·Molecular and Cellular Biology·J ZhouB Futcher
Jun 3, 2000·The EMBO Journal·H SeimiyaT Tsuruo

❮ Previous
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Citations

Nov 13, 2008·Cytotechnology·Dominique Broccoli
Oct 7, 2011·Protein & Cell·Craig NichollsJun-Ping Liu
Aug 14, 2003·Experimental Cell Research·Moses KimElizabeth H Blackburn
Apr 25, 2003·Lancet·Christopher M CounterCarolyn C Compton
May 22, 2003·Cancer Letters·Lea Harrington
Nov 6, 2002·Trends in Biochemical Sciences·Colleen KelleherJoachim Lingner
Apr 5, 2013·Nature·Jiansen JiangJuli Feigon
Apr 9, 2008·Nature Chemical Biology·David AlvesShankar Balasubramanian
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Kathleen Collins
Jan 10, 2013·Nature Reviews. Molecular Cell Biology·Jayakrishnan Nandakumar, Thomas R Cech
Feb 8, 2006·Nature Structural & Molecular Biology·Steven A JacobsThomas R Cech
Jul 9, 2002·The Plant Journal : for Cell and Molecular Biology·Katarzyna Heller-UszynskaAndrzej Kilian
Apr 9, 2005·The New England Journal of Medicine·Hiroki YamaguchiNeal S Young
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Shibani MukherjeeJames M Roberts
Mar 1, 2012·The Journal of Biological Chemistry·Barbara Eckert, Kathleen Collins
Apr 10, 2013·The Journal of Biological Chemistry·Meng HeVann Bennett
May 21, 2005·The Journal of Biological Chemistry·Neal F Lue
Jul 3, 2008·The Journal of Biological Chemistry·Brian D Freibaum, Christopher M Counter
Jan 17, 2003·Molecular Biology of the Cell·Katherine L FriedmanThomas R Cech
Sep 19, 2003·Molecular Biology of the Cell·Tracy M BryanThomas R Cech
Sep 18, 2002·Nucleic Acids Research·Libin WangDorothy E Shippen
Jul 11, 2003·Nucleic Acids Research·Sylvain HuardChantal Autexier
Jan 5, 2008·Nucleic Acids Research·Sharon N Finger, Tracy M Bryan
Nov 6, 2010·Nucleic Acids Research·Julie JurczylukTracy M Bryan
Mar 17, 2010·Genes & Development·Arthur J ZaugThomas R Cech
Aug 17, 2002·Genes & Development·Nesrin M HamadChristopher M Counter
Jun 4, 2008·Molecular and Cellular Biology·Katharine S BarrientosChristopher M Counter
May 2, 2012·Molecular and Cellular Biology·J Lewis SternTracy M Bryan
Feb 14, 2007·Molecular and Cellular Biology·Haley D M WyattTara L Beattie
Feb 15, 2012·Molecular and Cellular Biology·Tohru YonekawaChristopher M Counter
Aug 9, 2002·Molecular and Cellular Biology·Soma S R BanikChristopher M Counter
Apr 17, 2003·Molecular and Cellular Biology·Blaine N ArmbrusterChristopher M Counter
Apr 3, 2004·Molecular and Cellular Biology·Blaine N ArmbrusterChristopher M Counter
Oct 4, 2005·Molecular and Cellular Biology·Hong JiKatherine L Friedman
Sep 5, 2002·Microbiology and Molecular Biology Reviews : MMBR·Yu-Sheng CongJerry W Shay
Mar 23, 2011·Biochemistry. Biokhimii︠a︡·M I ZverevaO A Dontsova
Aug 18, 2006·Molekuliarnaia biologiia·D M ShcherbakovaO A Dontsova

❮ Previous
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