Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation
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Author
Wang, Lizhong
Liu, Runhua
Ye, Peiying
Wong, Chunshu
Chen, Guo-Yun
Sakabe, Kaoru
Zheng, Xincheng
Wu, Wei
Zhang, Peng
Jiang, Taijiao
Bassetti, Michael F.
Jube, Sandro
Sun, Yi
Zhang, Yanping
Zheng, Pan
Liu, Yang
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms6909Metadata
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Wang, L., R. Liu, P. Ye, C. Wong, G. Chen, P. Zhou, K. Sakabe, et al. 2015. “Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation.” Nature Communications 6 (1): 5909. doi:10.1038/ncomms6909. http://dx.doi.org/10.1038/ncomms6909.Abstract
CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300525/pdf/Terms of Use
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