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Inhibition of c‐Myc activity by ribosomal protein L11
Author(s) -
Dai MuShui,
Arnold Hugh,
Sun XiaoXin,
Sears Rosalie,
Lu Hua
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601776
Subject(s) - ribosome biogenesis , biology , ribosomal protein , ribosomal rna , rna polymerase i , microbiology and biotechnology , ribosome , rna , biochemistry , gene , rna polymerase
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.