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AlphaCP1 mediates stabilization of hTERT mRNA by autocrine human growth hormone

AlphaCP1 mediates stabilization of hTERT mRNA by autocrine human growth hormone
AlphaCP1 mediates stabilization of hTERT mRNA by autocrine human growth hormone
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, alphaCP1 and alphaCP2, 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.
0021-9258
680-690
Emerald, B. Starling
66510647-cb97-4d53-adee-4eb489989112
Chen, Yong
080582eb-3fa5-414c-bb62-1c60b2fe6498
Zhu, Tao
36d439b2-dc4a-4363-9ebb-ec2c387c4069
Zhu, Zhe
c51762d2-e6c5-4657-9300-c94387028288
Lee, Kok-Onn
9206cae6-dddb-4466-a3fb-d7fa7a7c2fdc
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Lobie, Peter E.
1b5a20a1-8373-4bf1-8af2-d71bfe5b8603
Emerald, B. Starling
66510647-cb97-4d53-adee-4eb489989112
Chen, Yong
080582eb-3fa5-414c-bb62-1c60b2fe6498
Zhu, Tao
36d439b2-dc4a-4363-9ebb-ec2c387c4069
Zhu, Zhe
c51762d2-e6c5-4657-9300-c94387028288
Lee, Kok-Onn
9206cae6-dddb-4466-a3fb-d7fa7a7c2fdc
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Lobie, Peter E.
1b5a20a1-8373-4bf1-8af2-d71bfe5b8603

Emerald, B. Starling, Chen, Yong, Zhu, Tao, Zhu, Zhe, Lee, Kok-Onn, Gluckman, Peter D. and Lobie, Peter E. (2007) AlphaCP1 mediates stabilization of hTERT mRNA by autocrine human growth hormone. The Journal of Biological Chemistry, 282 (1), 680-690. (doi:10.1074/jbc.M600224200).

Record type: Article

Abstract

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, alphaCP1 and alphaCP2, 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.

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Published date: 5 January 2007

Identifiers

Local EPrints ID: 61090
URI: http://eprints.soton.ac.uk/id/eprint/61090
ISSN: 0021-9258
PURE UUID: 4d3f8b54-f9b7-48f6-973e-13bf0f5216ea

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Date deposited: 25 Sep 2008
Last modified: 15 Mar 2024 11:22

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Contributors

Author: B. Starling Emerald
Author: Yong Chen
Author: Tao Zhu
Author: Zhe Zhu
Author: Kok-Onn Lee
Author: Peter D. Gluckman
Author: Peter E. Lobie

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