PMID- 23128672
OWN - NLM
STAT- MEDLINE
DCOM- 20140109
LR  - 20201109
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 29
IP  - 1
DP  - 2013 Jan
TI  - Downregulation of ubiquitin E3 ligase TNF receptor-associated factor 7 leads to 
      stabilization of p53 in breast cancer.
PG  - 283-7
LID - 10.3892/or.2012.2121 [doi]
AB  - 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.
FAU - Wang, Lixin
AU  - Wang L
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, PR China.
FAU - Wang, Lei
AU  - Wang L
FAU - Zhang, Shuping
AU  - Zhang S
FAU - Qu, Guangbo
AU  - Qu G
FAU - Zhang, Daoqiang
AU  - Zhang D
FAU - Li, Shitao
AU  - Li S
FAU - Liu, Sijin
AU  - Liu S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121101
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Messenger)
RN  - 0 (TP53 protein, human)
RN  - 0 (TRAF7 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Ubiquitin)
SB  - IM
MH  - Biomarkers, Tumor/*analysis
MH  - Breast Neoplasms/genetics/metabolism/*mortality
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Mutation/genetics
MH  - Neoplasm Grading
MH  - Prognosis
MH  - Protein Stability
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Rate
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/*antagonists & 
      inhibitors/genetics/metabolism
MH  - Tumor Suppressor Protein p53/*chemistry/genetics/metabolism
MH  - Ubiquitin/*metabolism
MH  - Ubiquitination
EDAT- 2012/11/07 06:00
MHDA- 2014/01/10 06:00
CRDT- 2012/11/07 06:00
PHST- 2012/08/31 00:00 [received]
PHST- 2012/09/28 00:00 [accepted]
PHST- 2012/11/07 06:00 [entrez]
PHST- 2012/11/07 06:00 [pubmed]
PHST- 2014/01/10 06:00 [medline]
AID - 10.3892/or.2012.2121 [doi]
PST - ppublish
SO  - Oncol Rep. 2013 Jan;29(1):283-7. doi: 10.3892/or.2012.2121. Epub 2012 Nov 1.