PMID- 10197982
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 7
DP  - 1999 Apr 1
TI  - Functional requirement of p23 and Hsp90 in telomerase complexes.
PG  - 817-26
AB  - Most normal human diploid cells have no detectable telomerase; however,
      expression of the catalytic subunit of telomerase is sufficient to induce
      telomerase activity and, in many cases, will bypass normal senescence. We and
      others have previously demonstrated in vitro assembly of active telomerase by
      combining the purified RNA component with the reverse transcriptase catalytic
      component synthesized in rabbit reticulocyte extract. Here we show that assembly 
      of active telomerase from in vitro-synthesized components requires the
      contribution of proteins present in reticulocyte extracts. We have identified the
      molecular chaperones p23 and Hsp90 as proteins that bind to the catalytic subunit
      of telomerase. Blockade of this interaction inhibits assembly of active
      telomerase in vitro. Also, a significant fraction of active telomerase from cell 
      extracts is associated with p23 and Hsp90. Consistent with in vitro results,
      inhibition of Hsp90 function in cells blocks assembly of active telomerase. To
      our knowledge, p23 and Hsp90 are the first telomerase-associated proteins
      demonstrated to contribute to telomerase activity.
FAU - Holt, S E
AU  - Holt SE
AD  - Department of Cell Biology and Neuroscience, University of Texas (UT)
      Southwestern Medical Center, Dallas, Texas 75235 USA.
FAU - Aisner, D L
AU  - Aisner DL
FAU - Baur, J
AU  - Baur J
FAU - Tesmer, V M
AU  - Tesmer VM
FAU - Dy, M
AU  - Dy M
FAU - Ouellette, M
AU  - Ouellette M
FAU - Trager, J B
AU  - Trager JB
FAU - Morin, G B
AU  - Morin GB
FAU - Toft, D O
AU  - Toft DO
FAU - Shay, J W
AU  - Shay JW
FAU - Wright, W E
AU  - Wright WE
FAU - White, M A
AU  - White MA
LA  - eng
GR  - R01 AG007992/AG/NIA NIH HHS/United States
GR  - AG07992/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Benzoquinones)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Quinones)
RN  - 0 (protein p23)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - EC 2.7.7.49 (Telomerase)
RN  - Z3K3VJ16KU (geldanamycin)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Benzoquinones
MH  - Blotting, Western
MH  - Cyclosporine/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Lactams, Macrocyclic
MH  - Molecular Chaperones/metabolism
MH  - Quinones/metabolism
MH  - RNA-Directed DNA Polymerase/metabolism
MH  - Rabbits
MH  - Reticulocytes/metabolism
MH  - Telomerase/*metabolism
MH  - Time Factors
PMC - PMC316592
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1101/gad.13.7.817 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Apr 1;13(7):817-26. doi: 10.1101/gad.13.7.817.