Abstract
silencing by siCUGBP1 reduced its binding to the CDK4 mRNA, promoted its translation, and induced CDK4 protein levels. Polyamines function as biological regulators of normal intestinal mucosal growth, and decreasing cellular polyamine depletion by inhibiting ornithine decarboxylase (key enzyme for polyamine biosynthesis) resulted in G1 phase growth arrest. Polyamine depletion also increased cytoplasmic CUGBP1 levels, which was associated with a repression of CDK4 mRNA translation. Increased cytoplasmic CUGBP1 by polyamine depletion bound to the CDK4 mRNA through direct interaction with its 3'-UTR and CR. CUGBP1 silencing by siCUGBP1 decreased [CUGBP1/CDK4 mRNA] complex and enhanced CDK4 translation, thus inducing CDK4 protein levels and promoting cell proliferation in polyamine-deficient cells. Conclusions: These results indicate that 1) CUGBP1 negatively regulates CDK4 mRNA translation in normal IECs through interaction with CDK4 mRNA and 2) CUGBP1-mediated repression of CDK4 translation plays an important role in growth inhibition following polyamine depletion.
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