Nuclear ErbB-2 enhances translation and cell growth by activation of rRNA gene transcription.

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16198

Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16198

Title:	Nuclear ErbB-2 enhances translation and cell growth by activation of rRNA gene transcription.
Authors:	李龍緣;Li, Long-Yuan;Lai, C-C.;佘玉萍;Sher, Y-P.;Lien, H-C.;Tsai, C-H.
Contributors:	生物科技學系
Keywords:	ErbB-2;ribosomal RNA;RNA polymerase I;translation
Date:	2011
Issue Date:	2012-11-23 17:09:48 (UTC+8)
Abstract:	Aberrant regulation of ribosomal RNA (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 β-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. RNAi-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 which is defective in nuclear translocation. Chromatin immunoprecipitation assays revealed that ErbB2 enhances binding of RNA Pol I to rDNA. Additionally, ErbB2 associated with rDNA, RNA Pol I and β-actin, suggesting how it could stimulate rRNA production, protein synthesis and increased cell size and cell growth. Lastly, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK, 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.
Relation:	CANCER RESEARCH
Appears in Collections:	[生物科技學系] 期刊論文

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