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.
Emerald
B Starling
BS
Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
Chen
Yong
Y
Zhu
Tao
T
Zhu
Zhe
Z
Lee
Kok-Onn
KO
Gluckman
Peter D
PD
Lobie
Peter E
PE
D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000737:chemistry*; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000737:chemistry* / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation
D020413:3' Untranslated Regions; C501903:PCBP2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019382:Human Growth Hormone; D019098:Telomerase