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Amyloid-β precursor-like protein APLP1 is a novel p53 transcriptional target gene that augments neuroblastoma cell death upon genotoxic stress

Oncogene volume 26, pages 7302–7312 (2007)Cite this article

Abstract

The tumor suppressor p53 is a key modulator of the cellular stress response, inducing cell-cycle arrest, apoptosis, senescence and cell differentiation. To evaluate further the molecular mechanism underlying p53 function, the transcriptional profiles of proliferating and senescent WI-38 cells, both wild-type p53 expressers and counterparts with an inactivated p53, were compared by DNA microarray analysis. In particular, the amyloid-β precursor-like protein 1 (APLP1) is induced in senescent cells in a p53-dependent manner. APLP1 was confirmed to be a novel transcriptional target of p53 by in vivo and in vitro characterization of a p53 responsive element found in the first intron of the APLP1 gene locus. APLP1 knockdown experiments demonstrate that APLP1 is required for the proliferation of fibroblastic and epithelial cells. Moreover, depletion of APLP1 expression diminishes stress-induced apoptosis of neural cells, whereas ectopic APLP1 expression augments apoptosis. Based on these data, a mechanism is proposed whereby p53-dependent induction of APLP1 is involved in neural cell death, and which may exacerbate neuronal cell loss in some acute or chronic neurodegenerative disorders.

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Acknowledgements

This research was supported by a Center of Excellence grant from the Flight Attendant Medical Research Institute (FAMRI), EC FP6 grant LSHC-CT-2004-503576 and Yad Abraham Center for Cancer Diagnosis and Therapy. This publication reflects our views and not necessarily those of the European Community. The EC is not liable for any use that may be made of the information contained herein. VR is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann Institute.

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  1. Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel

    X Tang, M Milyavsky, N Goldfinger & V Rotter

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  1. X Tang
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  4. V Rotter
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Correspondence to V Rotter.

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Supplementary Information accompanies the paper on the Oncogene Web site (http://www.nature.com/onc).

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Tang, X., Milyavsky, M., Goldfinger, N. et al. Amyloid-β precursor-like protein APLP1 is a novel p53 transcriptional target gene that augments neuroblastoma cell death upon genotoxic stress. Oncogene 26, 7302–7312 (2007). https://doi.org/10.1038/sj.onc.1210542

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