Interaction between human angiogenin and the p53 TAD2 domain and its implication for inhibitor discovery

Interaction between angiogenin and the p53 TAD2 domain in cancer cells can inhibit the function of the p53 tumor suppressor and promote cell survival. Based on a model structure using NMR and mutational analysis, positively charged 31RRR33 and 50KRSIK54 motifs of human angiogenin were identified as...

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Bibliographic Details
Published in:FEBS letters 2017-12, Vol.591 (23), p.3916-3925
Main Authors: Yeo, Kwon Joo, Jee, Jun‐Goo, Hwang, Eunha, Kim, Eun‐Hee, Jeon, Young Ho, Cheong, Hae‐Kap
Format: Article
Language:English
Subjects:
angiogenesis
Angiogenin
p53
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Summary:Interaction between angiogenin and the p53 TAD2 domain in cancer cells can inhibit the function of the p53 tumor suppressor and promote cell survival. Based on a model structure using NMR and mutational analysis, positively charged 31RRR33 and 50KRSIK54 motifs of human angiogenin were identified as p53‐binding sites that could interact with negatively charged D48/E51 and E56 residues of the p53 TAD2 domain, respectively. These results suggest that 31RRR33 and 50KRSIK54 motifs of human angiogenin might play a critical role in the regulation of p53‐mediated apoptosis and angiogenesis in cancer cells. This study identifies potential target sites for screening angiogenin‐specific inhibitors that could not only inhibit p53 binding but could also simultaneously inhibit cell binding, internalization, DNA binding, and nuclear translocation of human angiogenin.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12899