Feedback regulation of c-Myc by ribosomal protein L11.
Several ribosomal proteins including L11 have been shown to activate p53 by inhibiting oncoprotein MDM2, leading to inhibition of cell cycle progression. Our recent study showed that L11 also inhibits oncoprotein c-Myc. Overexpression of L11 inhibits c-Myc-induced transcription and cell proliferation, while reduction of endogenous L11 increases these c-Myc activities. Interestingly, L11 is a transcriptional target of c-Myc, thus forming a negative feedback loop. We further showed that L11 competes with coactivator TRRAP for binding to c-Myc through the Myc box II (MB II) and reduces histone H4 acetylation at c-Myc target gene promoters. In addition, L11 appears to regulate c-Myc levels. Knocking down L11 markedly increases the mRNA and protein levels of endogenous c-Myc. These results suggest that L11 also inhibits cell cycle progression by regulating the c-Myc pathway. Here we further discuss the implications of this regulation and questions that this finding raises.
Dai
Mu-Shui
MS
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Sears
Rosalie
R
Lu
Hua
H
D000818:Animals; D025461:Feedback, Physiological / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000502:physiology*
D006131:Growth Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012269:Ribosomal Proteins; C027624:ribosomal protein L11