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eIF4E-Overexpression imparts perillyl alcohol and rapamycin-mediated regulation of telomerase reverse transcriptase.

Abstract：

:Translation is mediated partly by regulation of free eukaryotic initiation factor 4E (eIF4E) levels through PI3K-Akt-mTOR signaling. Cancer cells treated with the plant-derived perillyl alcohol (POH) or the mechanistic target of rapamycin (mTOR) inhibitor rapamycin dephosphorylate eIF4E-binding protein (4E-BP1) and attenuate cap-dependent translation. We previously showed in cancer cell lines with elevated eIF4E that POH and rapamycin regulate telomerase activity through this pathway. Here, immortalized Chinese hamster ovary (CHO) control cells and CHO cells with forced eIF4E expression (rb4E) were used to elucidate eIF4E's role in telomerase regulation by POH and rapamycin. Despite 5-fold higher eIF4E amounts in rb4E, telomerase activity, telomerase reverse transcriptase (TERT) mRNA, and TERT protein were nearly equivalent in control and rb4E cells. In control cells, telomerase activity, TERT mRNA and protein levels were unaffected by either compound. In contrast, telomerase activity and TERT protein were both attenuated by either agent in rb4E cells, but without corresponding TERT mRNA decreases indicating a translational/post-translational process. S6K, Akt, and 4E-BP1 were modulated by mTOR mediators only in the presence of increased eIF4E. Thus, eIF4E-overexpression in rb4E cells enables inhibitory effects of POH and rapamycin on telomerase and TERT protein. Importantly, eIF4E-overexpression modifies cellular protein synthetic processes and gene regulation.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Sundin T,Peffley D,Hentosh P

doi

10.1016/j.yexcr.2013.05.029

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

2103-2112

issue

13

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(13)00247-4

journal_volume

319

pub_type

杂志文章

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