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J. Biol. Chem., Vol. 282, Issue 1, 680-690, January 5, 2007

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CP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone^*

B. Starling Emerald¹, Yong Chen¹, Tao Zhu, Zhe Zhu^¶, Kok-Onn Lee^¶, Peter D. Gluckman, and Peter E. Lobie²

From the Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand, the ^¶Department of Medicine, National University of Singapore 117609, Republic of Singapore, and the Institute of Molecular and Cell Biology, Singapore 117609, Republic of Singapore

We herein demonstrate that autocrine human growth hormone production in human mammary carcinoma cells results in increased telomerase activity as a result of specific up-regulation of telomerase catalytic subunit (human telomerase reverse transcriptase (hTERT)) mRNA and protein. This increase in hTERT gene expression is not due to increased transcriptional activation of the hTERT promoter but is the result of increased stability of hTERT mRNA exerted by CU-rich cis-regulatory sequences present in the 3'-untranslated region of TERT mRNA. Autocrine human growth hormone up-regulates two poly(C)-binding proteins, CP1 and CP2, which bind to these cis-regulatory elements and stabilize hTERT mRNA. We have therefore demonstrated that post-transcriptional modulation of the level of hTERT mRNA is one mechanism for regulation of cellular telomerase activity.

Received for publication, January 10, 2006 , and in revised form, November 3, 2006.

^* This work was supported by grants from the National Research Centre for Growth and Development, New Zealand (Theme 2) and The Marsden Fund, Royal Society of New Zealand. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this work.

² To whom correspondence should be addressed: Liggins Institute, University of Auckland, 2-6 Park Ave., Private Bag 92019, Auckland, New Zealand. Tel.: 64-9-3737599, Ext. 82125; Fax: 64-9-3737497; E-mail: p.lobie{at}auckland.ac.nz.

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