Regulation of p53 level by UBE4B in breast cancer

• Published in: PloS one 2014-02, Vol.9 (2), p.e90154
• Main Authors: Zhang, Ying, Lv, Yanrong, Zhang, Yongyang, Gao, Haidong
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Apoptosis; Biology; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Carcinogenesis; Cell cycle; Cell growth; Cell Line, Tumor; Cell survival; Degradation; Enzymes; Female; Fluorides; Gene amplification; Gene Expression Regulation, Neoplastic; Health aspects; Humans; Immunoglobulins; Ligases; Medicine; Mice; Neuroblastoma; p53 Protein; Plasmids; Proteasomes; Proteins; Proteolysis; Proto-Oncogene Proteins c-mdm2 - metabolism; Stability; Surgery; Tumor proteins; Tumor suppressor genes; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; Tumorigenesis; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligase Complexes - metabolism; Ubiquitination
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090154

p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.