Vaults and Telomerase Share a Common Subunit, TEP1*
- Valerie A. Kickhoefer‡§,
- Andrew G. Stephen‡,
- Lea Harrington¶,
- Murray O. Robinson‖ and
- Leonard H. Rome‡
- From the ‡Department of Biological Chemistry, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, the ¶Ontario Cancer Institute-Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada, and ‖Amgen, Inc., Thousand Oaks, California 91320
Abstract
Vaults are large cytoplasmic ribonucleoprotein complexes of undetermined function. Mammalian vaults have two high molecular mass proteins of 193 and 240 kDa. We have identified a partial cDNA encoding the 240-kDa vault protein and determined it is identical to the mammalian telomerase-associated component, TEP1. TEP1 is the mammalian homolog of the Tetrahymena p80 telomerase protein and has been shown to interact specifically with mammalian telomerase RNA and the catalytic protein subunit hTERT. We show that while TEP1 is a component of the vault particle, vaults have no detectable telomerase activity. Using a yeast three-hybrid assay we demonstrate that several of the human vRNAs interact in a sequence-specific manner with TEP1. The presence of 16 WD40 repeats in the carboxyl terminus of the TEP1 protein is a convenient number for this protein to serve a structural or organizing role in the vault, a particle with eight-fold symmetry. The sharing of the TEP1 protein between vaults and telomerase suggests that TEP1 may play a common role in some aspect of ribonucleoprotein structure, function, or assembly.
Footnotes
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↵* This work was supported by a United States Public Health Service grant from the National Institutes of Health (GM38097) and a grant from the Margaret E. Early Foundation (to L. H. R.) and by a grant from the Medical Research Council of Canada (to L. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom inquiries should be addressed: 33–257 CHS, Dept. of Biological Chemistry, UCLA School of Medicine, Los Angeles, CA 90095-1737. Tel.: 310-825-0397; Fax: 310-206-5272; E-mail: vkick@mednet.ucla.edu.
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↵2 V. Kickhoefer and L. Rome, unpublished data.
- Abbreviations:
- MVP
-
major vault protein
- TEP1
-
telomerase associated protein 1
- vRNA
-
vault RNA
- TERT
-
telomerase reverse transcriptase
- MDR
-
multidrug resistance
- TRAP
-
telomere repeat amplification
- TER
-
telomerase RNA
- RNP
-
ribonucleoprotein
- PCR
-
polymerase chain reaction
- kb
-
kilobase(s)
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- Received June 8, 1999.
- Revision received August 16, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
