MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles.
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 SUI1 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 oncogenesis.
Reinert
Line S
LS
University of Maryland, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Shi
Bo
B
Nandi
Suvobroto
S
Mazan-Mamczarz
Krystyna
K
Vitolo
Michele
M
Bachman
Kurtis E
KE
He
Huili
H
Gartenhaus
Ronald B
RB
D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D018797:Cell Cycle Proteins; C112641:DENR protein, human; C410108:EIF1 protein, human; D039642:Eukaryotic Initiation Factors; C115081:MCTS1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D012315:RNA Caps