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

Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guoyun Chen, Penghui Zhou, Kaoru Sakabe, Xincheng Zheng, Wei Wu, Peng Zhang, Taijiao Jiang, Michael F. Bassetti, Sandro Jube, Yi Sun, Yanping Zhang, Pan Zheng, Yang Liu

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Article number5909
JournalNature Communications
Volume6
DOIs
StatePublished - Jan 20 2015

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oncogenes
Viral Tumor Antigens
Viruses
Oncogenes
Papillomaviridae
deactivation
Small Interfering RNA
Tumors
Prostatic Neoplasms
Genes
cancer
antigens
mutations
Virus Inactivation
Polyomavirus Transforming Antigens
Antigens
Messenger RNA
Mutation
RNA Interference
tumor suppressor genes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation. / Wang, Lizhong; Liu, Runhua; Ye, Peiying; Wong, Chunshu; Chen, Guoyun; Zhou, Penghui; Sakabe, Kaoru; Zheng, Xincheng; Wu, Wei; Zhang, Peng; Jiang, Taijiao; Bassetti, Michael F.; Jube, Sandro; Sun, Yi; Zhang, Yanping; Zheng, Pan; Liu, Yang.

In: Nature Communications, Vol. 6, 5909, 20.01.2015.

Research output: Contribution to journalArticle

Wang, L, Liu, R, Ye, P, Wong, C, Chen, G, Zhou, P, Sakabe, K, Zheng, X, Wu, W, Zhang, P, Jiang, T, Bassetti, MF, Jube, S, Sun, Y, Zhang, Y, Zheng, P & Liu, Y 2015, 'Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation', Nature Communications, vol. 6, 5909. https://doi.org/10.1038/ncomms6909
Wang, Lizhong ; Liu, Runhua ; Ye, Peiying ; Wong, Chunshu ; Chen, Guoyun ; Zhou, Penghui ; Sakabe, Kaoru ; Zheng, Xincheng ; Wu, Wei ; Zhang, Peng ; Jiang, Taijiao ; Bassetti, Michael F. ; Jube, Sandro ; Sun, Yi ; Zhang, Yanping ; Zheng, Pan ; Liu, Yang. / Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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AU - Sakabe, Kaoru

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AU - Jiang, Taijiao

AU - Bassetti, Michael F.

AU - Jube, Sandro

AU - Sun, Yi

AU - Zhang, Yanping

AU - Zheng, Pan

AU - Liu, Yang

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