AKT Promotes rRNA Synthesis and Cooperates with c-MYC to Stimulate Ribosome Biogenesis in Cancer

Sci. Signal.  30 Aug 2011:
Vol. 4, Issue 188, pp. ra56
DOI: 10.1126/scisignal.2001754

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Building the Building Blocks

Ribosomes translate mRNA into protein, and the activity of signaling pathways that promote ribosome formation (or biogenesis) is often increased in cancer cells, which have high rates of protein synthesis and cell growth. Thus, each step of ribosome biogenesis can limit cell growth, including the synthesis of ribosomal RNA (rRNA), which encodes the RNA components of the ribosome. Chan et al. found that the kinase AKT, which is frequently activated in cancer cells and was previously implicated in promoting protein translation, also promotes rRNA synthesis. Cells with increased AKT activity showed increased rRNA abundance and more ribosomes. The transcription factor c-MYC is required for ribosome biogenesis, and the gene encoding c-MYC is frequently mutated in tumors. The ability of c-MYC to promote ribosome biogenesis and cell growth in a mouse model of lymphoma was attenuated by an AKT inhibitor. These results suggest that reducing ribosome biogenesis may in part underlie the therapeutic efficacy of anticancer drugs that target AKT signaling.