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

分类： 生物学 >> 生物物理学 提交时间： 2016-05-11

Wang, Lizhong Liu, Runhua Ye, Peiying Wong, Chunshu Chen, Guo-Yun Sakabe, Kaoru Jube, Sandro Zheng, Pan Liu, Yang Ye, Peiying Wong, Chunshu Chen, Guo-Yun Sakabe, Kaoru Jube, Sandro Zheng, Pan Liu, Yang Ye, Peiying Zhou, Penghui Zheng, Xincheng Wu, Wei

摘要： 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.

同行评议状态:待评议

 点击量 2531  下载量 1305  评论