MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles

被引:41
作者
Reinert, Line S.
Shi, Bo
Nandi, Suvobroto
Mazan-Mamczarz, Krystyna
Vitolo, Michele
Bachman, Kurtis E.
He, Huili
Gartenhaus, Ronald B.
机构
[1] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[2] NIA, Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA
[3] Northwestern Univ, Freinberg Sch Med, Dept Med, Div Rheumatol, Chicago, IL 60611 USA
关键词
D O I
10.1158/0008-5472.CAN-06-1999
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SU11 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and onco-genesis.
引用
收藏
页码:8994 / 9001
页数:8
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