Expression of proviral integration site for Moloney murine leukemia virus 1 (Pim-1) is post-transcriptionally regulated by tristetraprolin in cancer cells
| Autor: | Young Joo Min, Chae Won Kim, Nal Ae Yoon, Mai-Tram Vo, Ji Young Lee, Wha Ja Cho, Chang Hoon Moon, Chae Yeong Lee, Jeong Woo Park, Hyun Hee Lee, Hong Kyeung Kim |
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| Rok vydání: | 2012 |
| Předmět: |
Regulation of gene expression
Three prime untranslated region Cell growth Kinase RNA Stability Tristetraprolin Cell Biology Serine threonine protein kinase Biology Biochemistry Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-pim-1 Apoptosis hemic and lymphatic diseases Neoplasms Cancer cell Cancer research Humans Gene Regulation RNA Neoplasm Phosphorylation Molecular Biology 3' Untranslated Regions HeLa Cells |
| Zdroj: | The Journal of biological chemistry. 287(34) |
| ISSN: | 1083-351X |
| Popis: | The proviral integration site for Moloney murine leukemia virus 1 (Pim-1) is an oncogenic serine/threonine kinase that is up-regulated in several human cancers, facilitates cell cycle progression, and suppresses apoptosis. Previously, it has been reported that the Pim-1 3′-UTR plays important roles in the regulation of Pim-1 mRNA stability. However, the mechanisms explaining how Pim-1 mRNA stability is determined by its 3′-UTR are not well known. Here, we demonstrate that tristetraprolin (TTP) plays a critical role in the regulation of Pim-1 mRNA stability. Our results show that the level of Pim-1 expression is inversely correlated with TTP expression in human cancer cells. Pim-1 mRNA contains two AU-rich elements (ARE1 and ARE2) in the 3′-UTR. TTP bound to ARE2 and enhanced the decay of Pim-1 mRNA. Overexpression of TTP decreased Pim-1 expression and p21 and p27 phosphorylation and inhibited cell growth. Overexpression of Pim-1 cDNA without the 3′-UTR attenuated the inhibitory effects of TTP on p21 phosphorylation and cell growth. In addition, inhibition of p21 by siRNA attenuated the inhibitory effect of TTP on cell growth. Our results suggest that TTP post-transcriptionally down-regulates Pim-1 expression and that the overexpression of TTP may contribute to tumor suppression in part by down-regulating Pim-1 expression. |
| Databáze: | OpenAIRE |
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