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Cell Death Dis. 2012 Apr 19;3:e298. doi: 10.1038/cddis.2012.33.

Wig-1, a novel regulator of N-Myc mRNA and N-Myc-driven tumor growth.

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  • 1Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE-171 76, Sweden.

Abstract

Wig-1 is a transcriptional target of the p53 tumor suppressor and encodes an mRNA stability-regulating protein. We show here that Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc. Transient Wig-1 knockdown significantly delays development of N-Myc-driven tumors in mice. We also show that N-Myc expression is induced upon moderate p53-activating stress, suggesting a role of the p53-Wig-1-N-Myc axis in promoting cell cycle re-entry upon p53-induced cell cycle arrest and DNA repair. Moreover, our findings raise possibilities for the improved treatment of poor prognosis neuroblastomas that carry amplified N-Myc.

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