Abstract
Although Niban is highly expressed in human cancer cells, the cellular functions of Niban remain largely unknown. We demonstrate here that ultraviolet irradiation induces phosphorylation of Niban at S602 by AKT, which increases the association of Niban with nucleophosmin and disassociation of nucleophosmin from the MDM2 complex. This leads to the promotion of MDM2-p53 interaction and subsequent p53 degradation, thereby providing an antiapoptotic effect. Conversely, depletion of or deficiency in Niban expression promotes stabilization of p53 with increased cell apoptosis. Our findings illustrate a pivotal role for AKT-mediated phosphorylation of Niban in protecting cells from genotoxic stress-induced cell apoptosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Apoptosis*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cell Line, Tumor
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Cell Survival / radiation effects
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Humans
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / metabolism*
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Nucleophosmin
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Phosphorylation
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Protein Binding
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Protein Processing, Post-Translational
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Protein Stability
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Proto-Oncogene Proteins c-akt / metabolism*
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Proto-Oncogene Proteins c-mdm2 / metabolism*
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Serine / metabolism
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Tumor Suppressor Protein p53 / metabolism*
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Ultraviolet Rays
Substances
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Biomarkers, Tumor
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NIBAN1 protein, human
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NPM1 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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Nucleophosmin
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Serine
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
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Proto-Oncogene Proteins c-akt