Functional requirement of p23 and Hsp90 in telomerase complexes
- Shawn E. Holt,
- Dara L. Aisner,
- Joseph Baur,
- Valerie M. Tesmer,
- Marife Dy,
- Michel Ouellette,
- James B. Trager,
- Gregg B. Morin,
- David O. Toft,
- Jerry W. Shay,
- Woodring E. Wright, and
- Michael A. White
- Department of Cell Biology and Neuroscience, University of Texas (UT) Southwestern Medical Center, Dallas, Texas 75235 USA; Departments of Pathology and Human Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia 23998 USA; Geron Corporation, Menlo Park, California 94025 USA; Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota 55905 USA
Abstract
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.
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Footnotes
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↵Corresponding author.
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E-MAIL white08{at}utsw.swmed.edu; FAX (214) 648-8694.
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- Received November 24, 1998.
- Accepted February 19, 1999.
- Cold Spring Harbor Laboratory Press
