Inhibition of c-Myc activity by ribosomal protein L11.

The c-Myc oncoprotein promotes cell growth by enhancing ribosomal biogenesis through upregulation of RNA polymerases I-, II-, and III-dependent transcription. Overexpression of c-Myc and aberrant ribosomal biogenesis leads to deregulated cell growth and tumorigenesis. Hence, c-Myc activity and ribosomal biogenesis must be regulated in cells. Here, we show that ribosomal protein L11, a component of the large subunit of the ribosome, controls c-Myc function through a negative feedback mechanism. L11 is transcriptionally induced by c-Myc, and overexpression of L11 inhibits c-Myc-induced transcription and cell proliferation. Conversely, reduction of endogenous L11 by siRNA increases these c-Myc activities. Mechanistically, L11 binds to the Myc box II (MB II), inhibits the recruitment of the coactivator TRRAP, and reduces histone H4 acetylation at c-Myc target gene promoters. In response to serum stimulation or serum starvation, L11 and TRRAP display inverse promoter-binding profiles. In addition, L11 regulates c-Myc levels. These results identify L11 as a feedback inhibitor of c-Myc and suggest a novel role for L11 in regulating c-Myc-enhanced ribosomal biogenesis.