CUG-binding protein represses translation of p27Kip1 mRNA through its internal ribosomal entry site

Abstract

The cyclin dependent kinase inhibitor p27Kip1 plays an important role in controlling the eukaryotic cell cycle. The 5′-untranslated region of the p27 mRNA harbors an internal ribosome entry site (IRES ) which may facilitate synthesis of p27 in certain conditions. In this study, the RNA-associated protein CU GBP1 was shown to interact with the human p27 5′-untranslated region. Overexpression of CU GBP1 inhibited endogenous p27 expression and reduced translation initiation through the p27 IRES . In contrast, repression of CU GBP1 by siRNA transfection enhanced p27 protein levels and stimulated p27 IRES activity. Addition of recombinant CU GBP1 repressed p27 IRES reporter mRNA translation in vitro. At last, our finding showed that cytosolic form of CU GBP1 binds efficiently to the p27 5′-untranslated region. © 2011 Landes Bioscience.