Telomerase-Associated Protein TEP1 Is Not Essential for Telomerase Activity or Telomere Length Maintenance In Vivo

doi:10.1128/MCB.20.21.8178-8184.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Liu, Y.
	Articles by Harrington, L.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Liu, Y.
	Articles by Harrington, L.

Previous Article | Next Article

Molecular and Cellular Biology, November 2000, p. 8178-8184, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Telomerase-Associated Protein TEP1 Is Not Essential for Telomerase Activity or Telomere Length Maintenance In Vivo

Yie Liu,¹ Bryan E. Snow,¹ M. Prakash Hande,²^,³ Gabriela Baerlocher,² Valerie A. Kickhoefer,⁴ David Yeung,¹^,⁵ Andrew Wakeham,¹ Annick Itie,¹ David P. Siderovski,⁶ Peter M. Lansdorp,²^,⁷ Murray O. Robinson,⁵ and Lea Harrington¹^,^*

Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1,¹ Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, British Columbia V5Z 1L3,² and Department of Medicine, University of British Columbia, Vancouver, British Columbia,⁷ Canada; Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032³; Department of Biological Chemistry, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095⁴; Department of Pharmacology, UNC-CH School of Medicine, Chapel Hill, North Carolina⁶; and Amgen Inc., Thousand Oaks, California 91320⁵

Received 12 June 2000/Accepted 31 July 2000

TEP1 is a mammalian telomerase-associated protein with similarity to the Tetrahymena telomerase protein p80. Like p80, TEP1is associated with telomerase activity and the telomerase reversetranscriptase, and it specifically interacts with the telomeraseRNA. To determine the role of mTep1 in telomerase function invivo, we generated mouse embryonic stem (ES) cells and mice lackingmTep1. The mTep1-deficient (mTep1^/) mice were viable and were bred for seven successive generationswith no obvious phenotypic abnormalities. All murine tissues frommTep1^/ mice possessed a level of telomerase activity comparable to thatin wild-type mice. In addition, analysis of several tissues thatnormally lack telomerase activity revealed no reactivation oftelomerase activity in mTep1^/ mice. Telomere length, even in later generations of mTep1^/ mice, was equivalent to that in wild-type animals. ES cells deficientin mTep1 also showed no detectable alteration in telomerase activityor telomere length with increased passage in culture. Thus, mTep1appears to be completely dispensable for telomerase function invivo. Recently, TEP1 has been identified within a second ribonucleoprotein(RNP) complex, the vault particle. TEP1 can also specificallybind to a small RNA, vRNA, which is associated with the vaultparticle and is unrelated in sequence to mammalian telomeraseRNA. These results reveal that TEP1 is an RNA binding proteinthat is not restricted to the telomerase complex and that TEP1plays a redundant role in the assembly or localization of thetelomerase RNP invivo.

^* Corresponding author. Mailing address: Ontario Cancer Institute/Amgen Institute, 620 University Ave., Toronto, Ontario M5G2C1, Canada. Phone: (416) 204-2231. Fax: (416) 204-2277. E-mail:leah{at}oci.utoronto.ca.

Molecular and Cellular Biology, November 2000, p. 8178-8184, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Raval-Fernandes, S., Kickhoefer, V. A., Kitchen, C., Rome, L. H. (2005). Increased Susceptibility of Vault Poly(ADP-Ribose) Polymerase-Deficient Mice to Carcinogen-Induced Tumorigenesis. Cancer Res. 65: 8846-8852 [Abstract] [Full Text]
El-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A.-N., Ghedin, E., Worthey, E. A., Delcher, A. L., Blandin, G., Westenberger, S. J., Caler, E., Cerqueira, G. C., Branche, C., Haas, B., Anupama, A., Arner, E., Aslund, L., Attipoe, P., Bontempi, E., Bringaud, F., Burton, P., Cadag, E., Campbell, D. A., Carrington, M., Crabtree, J., Darban, H., da Silveira, J. F., de Jong, P., Edwards, K., Englund, P. T., Fazelina, G., Feldblyum, T., Ferella, M., Frasch, A. C., Gull, K., Horn, D., Hou, L., Huang, Y., Kindlund, E., Klingbeil, M., Kluge, S., Koo, H., Lacerda, D., Levin, M. J., Lorenzi, H., Louie, T., Machado, C. R., McCulloch, R., McKenna, A., Mizuno, Y., Mottram, J. C., Nelson, S., Ochaya, S., Osoegawa, K., Pai, G., Parsons, M., Pentony, M., Pettersson, U., Pop, M., Ramirez, J. L., Rinta, J., Robertson, L., Salzberg, S. L., Sanchez, D. O., Seyler, A., Sharma, R., Shetty, J., Simpson, A. J., Sisk, E., Tammi, M. T., Tarleton, R., Teixeira, S., Van Aken, S., Vogt, C., Ward, P. N., Wickstead, B., Wortman, J., White, O., Fraser, C. M., Stuart, K. D., Andersson, B. (2005). The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease. Science 309: 409-415 [Abstract] [Full Text]
Poderycki, M. J., Rome, L. H., Harrington, L., Kickhoefer, V. A. (2005). The p80 homology region of TEP1 is sufficient for its association with the telomerase and vault RNAs, and the vault particle. Nucleic Acids Res 33: 893-902 [Abstract] [Full Text]
Lee, G. E., Yu, E. Y., Cho, C. H., Lee, J., Muller, M. T., Chung, I. K. (2004). DNA-Protein Kinase Catalytic Subunit-interacting Protein KIP Binds Telomerase by Interacting with Human Telomerase Reverse Transcriptase. J. Biol. Chem. 279: 34750-34755 [Abstract] [Full Text]
Liu, Y., Snow, B. E., Kickhoefer, V. A., Erdmann, N., Zhou, W., Wakeham, A., Gomez, M., Rome, L. H., Harrington, L. (2004). Vault Poly(ADP-Ribose) Polymerase Is Associated with Mammalian Telomerase and Is Dispensable for Telomerase Function and Vault Structure In Vivo. Mol. Cell. Biol. 24: 5314-5323 [Abstract] [Full Text]
Hahn, W. C. (2003). Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer. JCO 21: 2034-2043 [Abstract] [Full Text]
Mossink, M. H., van Zon, A., Franzel-Luiten, E., Schoester, M., Kickhoefer, V. A., Scheffer, G. L., Scheper, R. J., Sonneveld, P., Wiemer, E. A. C. (2002). Disruption of the Murine Major Vault Protein (MVP/LRP) Gene Does Not Induce Hypersensitivity to Cytostatics. Cancer Res. 62: 7298-7304 [Abstract] [Full Text]
Chai, W., Ford, L. P., Lenertz, L., Wright, W. E., Shay, J. W. (2002). Human Ku70/80 Associates Physically with Telomerase through Interaction with hTERT. J. Biol. Chem. 277: 47242-47247 [Abstract] [Full Text]
Kickhoefer, V. A., Poderycki, M. J., Chan, E. K. L., Rome, L. H. (2002). The La RNA-binding Protein Interacts with the Vault RNA and Is a Vault-associated Protein. J. Biol. Chem. 277: 41282-41286 [Abstract] [Full Text]
Cong, Y.-S., Wright, W. E., Shay, J. W. (2002). Human Telomerase and Its Regulation. Microbiol. Mol. Biol. Rev. 66: 407-425 [Abstract] [Full Text]
Mergny, J.-L., Riou, J.-F., Mailliet, P., Teulade-Fichou, M.-P., Gilson, E. (2002). Natural and pharmacological regulation of telomerase. Nucleic Acids Res 30: 839-865 [Abstract] [Full Text]
Mason, D. X., Autexier, C., Greider, C. W. (2001). Tetrahymena proteins p80 and p95 are not core telomerase components. Proc. Natl. Acad. Sci. USA 10.1073/pnas.221456398v1 [Abstract] [Full Text]
Beattie, T. L., Zhou, W., Robinson, M. O., Harrington, L. (2001). Functional Multimerization of the Human Telomerase Reverse Transcriptase. Mol. Cell. Biol. 21: 6151-6160 [Abstract] [Full Text]
Kickhoefer, V. A., Liu, Y., Kong, L. B., Snow, B. E., Stewart, P. L., Harrington, L., Rome, L. H. (2001). The Telomerase/Vault-associated Protein TEP1 Is Required for Vault RNA Stability and Its Association with the Vault Particle. J. Cell Biol. 152: 157-164 [Abstract] [Full Text]
Mason, D. X., Autexier, C., Greider, C. W. (2001). Tetrahymena proteins p80 and p95 are not core telomerase components. Proc. Natl. Acad. Sci. USA 98: 12368-12373 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals