title: AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis.
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.
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Ji
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ding
authors.forename: David
authors.initials: D
authors.lastname: Hawke
authors.forename: Dongming
authors.initials: D
authors.lastname: Xing
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D020816:Amino Acid Motifs; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D051017:Apoptosis Regulatory Proteins
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D012694:Serine; D016159:Tumor Suppressor Protein p53; C516108:NIBAN1 protein, human; D051017:Apoptosis Regulatory Proteins; C000716967:NPM1 protein, human; C495901:TP53 protein, human; C497206:MDM2 protein, human