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AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis
Authors:Ji Haitao  Ding Zhiyong  Hawke David  Xing Dongming  Jiang Bing-Hua  Mills Gordon B  Lu Zhimin
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.
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.
Keywords:Niban   AKT   nucleophosmin   p53   MDM2   apoptosis
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