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Interaction between human angiogenin and the p53 TAD2 domain and its implication for inhibitor discovery
Author(s) -
Yeo Kwon Joo,
Jee JunGoo,
Hwang Eunha,
Kim EunHee,
Jeon Young Ho,
Cheong HaeKap
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12899
Subject(s) - angiogenin , chemistry , domain (mathematical analysis) , computational biology , microbiology and biotechnology , pharmacology , biology , cancer research , angiogenesis , mathematical analysis , mathematics
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 31 RRR 33 and 50 KRSIK 54 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 31 RRR 33 and 50 KRSIK 54 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.