Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation

Lizhong Wang (), Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, Kaoru Sakabe, Xincheng Zheng, Wei Wu, Peng Zhang, Taijiao Jiang, Michael F. Bassetti, Sandro Jube, Yi Sun, Yanping Zhang, Pan Zheng () and Yang Liu ()
Additional contact information
Lizhong Wang: University of Alabama at Birmingham
Runhua Liu: University of Alabama at Birmingham
Peiying Ye: Children’s Research Institute, Children’s National Medical Center
Chunshu Wong: Children’s Research Institute, Children’s National Medical Center
Guo-Yun Chen: Children’s Research Institute, Children’s National Medical Center
Penghui Zhou: Dana-Farber Cancer Institute, Harvard Medical School
Kaoru Sakabe: Children’s Research Institute, Children’s National Medical Center
Xincheng Zheng: OncoImmune, Inc.
Wei Wu: OncoImmune, Inc.
Peng Zhang: Institute of Biophysics, Chinese Academy of Science
Taijiao Jiang: Institute of Biophysics, Chinese Academy of Science
Michael F. Bassetti: School of Medicine, University of Michigan
Sandro Jube: Children’s Research Institute, Children’s National Medical Center
Yi Sun: School of Medicine, University of Michigan
Yanping Zhang: University of North Carolina
Pan Zheng: Children’s Research Institute, Children’s National Medical Center
Yang Liu: Children’s Research Institute, Children’s National Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms6909

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