Targeted suppression of MCT-1 attenuates the malignant phenotype through a translational mechanism.
The MCT-1 oncogene, highly expressed in a subset of non-Hodgkin's lymphomas interacts with the cap complex through its PUA domain. MCT-1 recruits DENR, a SUI1 motif containing protein that promotes translation initiation of cancer-related mRNAs. We reasoned that a PUA-domain mutant protein would repress MCT-1 function and attenuate the malignant phenotype. Human lymphoma cell lines expressing the PUA-domain mutant protein demonstrated reduced anchorage-independent growth and increased susceptibility to apoptosis. Significantly, we identified an altered translational profile in cells expressing the mutant protein. These data further buttress the role of the MCT-1 in lymphomagenesis and support the development of novel therapeutic strategies targeting MCT-1.
Mazan-Mamczarz
Krystyna
K
University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Hagner
Patrick
P
Dai
Bojie
B
Corl
Sharon
S
Liu
Zhenqui
Z
Gartenhaus
Ron B
RB
D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000209:etiology; D050505:Mutant Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects*
D018797:Cell Cycle Proteins; C112641:DENR protein, human; D039642:Eukaryotic Initiation Factors; C115081:MCTS1 protein, human; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins