Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes.

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Citation

Li LY, Chen H, Hsieh YH, Wang YN, Chu HJ, Chen YH, Chen HY, Chien PJ, Ma HT, Tsai HC, Lai CC, Sher YP, Lien HC, Tsai CH, Hung MC

Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes.

Cancer Res. 2011 Jun 15;71(12):4269-79. doi: 10.1158/0008-5472.CAN-10-3504. Epub 2011 May 9.

PubMed ID
21555369 [ View in PubMed
]
Abstract

Aberrant regulation of rRNA synthesis and translation control can facilitate tumorigenesis. The ErbB2 growth factor receptor is overexpressed in many human tumors and has been detected in the nucleus, but the role of nuclear ErbB2 is obscure. In this study, we defined a novel function of nuclear ErbB2 in enhancing rRNA gene transcription by RNA polymerase-I (RNA Pol I). Nuclear ErbB2 physically associates with beta-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. RNA interference-mediated knockdown of ErbB2 reduced pre-rRNA and protein synthesis. In contrast, wild-type ErbB2 augmented pre-rRNA level, protein production, and cell size/cell growth, but not by an ErbB2 mutant that is defective in nuclear translocation. Chromatin immunoprecipitation assays revealed that ErbB2 enhances binding of RNA Pol I to rDNA. In addition, ErbB2 associated with rDNA, RNA Pol I, and beta-actin, suggesting how it could stimulate rRNA production, protein synthesis, and increased cell size and cell growth. Finally, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK (extracellular signal regulated kinase), the main ErbB2 effector signaling pathways. Together, our findings indicate that nuclear ErbB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Receptor tyrosine-protein kinase erbB-2P04626Details
Actin, cytoplasmic 1P60709Details