Expression of proviral integration site for Moloney murine leukemia virus 1 (Pim-1) is post-transcriptionally regulated by tristetraprolin in cancer cells.
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.
Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
Hong Kyeung
HK
Kim
Chae Won
CW
Kim
Mai-Tram
MT
Vo
Hyun Hee
HH
Lee
Ji Young
JY
Lee
Nal Ae
NA
Yoon
Chae Yeong
CY
Lee
Chang Hoon
CH
Moon
Young Joo
YJ
Min
Jeong Woo
JW
Park
Wha Ja
WJ
Cho
D020413:3' Untranslated Regions; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1 / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D012334:RNA, Neoplasm; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1