Stable association of hsp90 and p23, but Not hsp70, with active human telomerase.
The ribonucleoprotein telomerase holoenzyme is minimally composed of a catalytic subunit, hTERT, and its associated template RNA component, hTR. We have previously found two additional components of the telomerase holoenzyme, the chaperones p23 and heat shock protein (hsp) 90, both of which are required for efficient telomerase assembly in vitro and in vivo. Both hsp90 and p23 bind specifically to hTERT and influence its proper assembly with the template RNA, hTR. We report here that the hsp70 chaperone also associates with hTERT in the absence of hTR and dissociates when telomerase is folded into its active state, similar to what occurs with other chaperone targets. Our data also indicate that hsp90 and p23 remain associated with functional telomerase complexes, which differs from other hsp90-folded enzymes that require only a transient hsp90.p23 binding. Our data suggest that components of the hsp90 chaperone complex, while required for telomerase assembly, remain associated with active enzyme, which may ultimately provide critical insight into the biochemical properties of telomerase assembly.
Departments of Pathology and Human Genetics, Massey Cancer Center, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0662, USA.
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Forsythe
J L
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Jarvis
J W
JW
Turner
L W
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Elmore
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SE
Holt
D001665:Binding Sites; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D012313:RNA; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry / Q000378:metabolism*; D013698:Templates, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C105998:Hsp23 protein, Drosophila; D011994:Recombinant Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase