Nucleophosmin interacts directly with c-Myc and controls c-Myc-induced hyperproliferation and transformation

被引:94
|
作者
Li, Zhaoliang [1 ]
Boone, David [1 ]
Hann, Stephen R. [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA
关键词
Myc; proliferation; NPM; B23;
D O I
10.1073/pnas.0806879105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The transcription factor c-Myc is essential for cellular proliferation and is one of the most frequently activated oncogenes, but the molecular mechanism mediating its critical role in transformation is unclear. Like c-Myc, multifunctional nucleophosmin (NPM) is tightly regulated during proliferation and is overexpressed in several different types of cancer. Overexpression of NPM enhances proliferation and oncogene-mediated transformation, but the mechanism mediating these effects is unknown. We examined whether NPM stimulates proliferation and transformation by affecting c-Myc. Here, we show that NPM is essential for the activities of oncogenic c-Myc and that overexpressed NPM dramatically stimulates c-Myc-induced hyperproliferation and transformation. Endogenous and exogenous NPM directly interact with c-Myc and regulate the expression of endogenous c-Myc target genes at the promoter. Therefore, NPM is a key cofactor for the transforming activity of c-Myc and the interaction with c-Myc may mediate the enhancement of proliferation and transformation induced by NPM overexppression.
引用
收藏
页码:18794 / 18799
页数:6
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