title: Downregulation of ubiquitin E3 ligase TNF receptor-associated factor             7 leads to stabilization of p53 in breast cancer.
abstract: p53 is a key tumor suppressor and a master regulator of various signaling             pathways, such as those related to apoptosis, cell cycle and DNA repair. In this             study, we found a pronounced cytosolic accumulation of the p53 protein in a panel             of breast cancer specimens. Several mutations lead to p53 accumulation by disruption             of MDM2-mediated p53 degradation. However, gene sequencing revealed no p53 mutation             in the majority of our samples. Through search for other possible p53 E3 ligases             by mRNA and protein expression analysis, downregulation of TNF receptor-associated             factor 7 (TRAF7) expression was found in these breast tumors. We further identified             TRAF7 as an E3 ligase for K48-linked ubiquitination of p53 in vitro. These results             suggested that the p53 accumulation was due to the defects of TRAF7-mediated ubiquitination.             The downregulation of TRAF7 also correlated with poor prognosis in a breast cancer             cohort. Collectively, TRAF7-mediated ubiquitination of p53 plays a critical role             in breast cancer development, and these insights may aid in the development of             novel therapeutic strategies for breast cancer.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.forename: Daoqiang
authors.initials: D
authors.lastname: Zhang
authors.forename: Shitao
authors.initials: S
authors.lastname: Li
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D011379:Prognosis; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C495901:TP53 protein, human; C486460:TRAF7 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin