Author/Authors :
Huang، نويسنده , , Sidong and Laoukili، نويسنده , , Jamila and Epping، نويسنده , , Mirjam T. and Koster، نويسنده , , Jan and Hِlzel، نويسنده , , Michael A. Westerman، نويسنده , , Bart A. and Nijkamp، نويسنده , , Wouter and Hata، نويسنده , , Akiko and Asgharzadeh، نويسنده , , Shahab and Seeger، نويسنده , , Robert C. and Versteeg، نويسنده , , Rogier and Beijersbergen، نويسنده , , Roderick L. and Bernards، نويسنده , , René، نويسنده ,
Abstract :
Summary
ids play key roles in differentiation, growth arrest, and apoptosis and are increasingly being used in the clinic for the treatment of a variety of cancers, including neuroblastoma. Here, using a large-scale RNA interference-based genetic screen, we identify ZNF423 (also known as Ebfaz, OAZ, or Zfp423) as a component critically required for retinoic acid (RA)-induced differentiation. ZNF423 associates with the RARα/RXRα nuclear receptor complex and is essential for transactivation in response to retinoids. Downregulation of ZNF423 expression by RNA interference in neuroblastoma cells results in a growth advantage and resistance to RA-induced differentiation, whereas overexpression of ZNF423 leads to growth inhibition and enhanced differentiation. Finally, we show that low ZNF423 expression is associated with poor disease outcome in neuroblastoma patients.
