New Study Reveals p53’s Functional Dependence on Cellular Context
Source:
Time: 2012-07-11
A research group led by Prof WU Jiarui from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences recently found out that cellular context can effect p53-regulatory network, rewiring the "master regulator" p53’s function in tumorgenesis.
Researchers from WU’s lab found that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent, 5-aza-2’-deoxycytidine (ZdCyd), whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment. Surprisingly, p53 activity was highly up-regulated by ZdCyd in both growing-conditions.
By working with Prof CHEN Luonan’s group, they built up a new computational approach revealed there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached-P19-cells, whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53-network in detached-P19-cells.
Using protein-protein interaction analysis, researchers realized that the network of the ZdCyd-treated detached-P19-cells was significantly different from that of ZdCyd-treated attached-P19-cells. On the other hand, inhibition of p53 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached-P19-cells, suggesting that the ZdCyd-activated p53 plays oncogenic function in detached-P19-cells.
Taken together, these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.
This work was supported by grants from Ministry of Science and Technology and National Natural Science Foundation of China, and was published online on June 1st, 2012 in Journal of Molecular Cell Biology.
AUTHOR CONTACT:
WU Jiarui
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Rewired p53-regulatory network in different cellular context. (Image provided by Dr. WU Jiarui)
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