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PMID: 22510990 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis.

EMBO reports ·Vol. 13 ·No. 6 ·2012-06-01 ·Pages 554-60

Ji H, Ding Z, Hawke D, Xing D, Jiang BH, Mills GB, Lu Z

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.

MeSH Terms
Amino Acid Motifs Apoptosis Biomarkers, Tumor/genetics,metabolism Cell Line, Tumor Cell Survival/radiation effects Humans Neoplasm Proteins/genetics,metabolism Nuclear Proteins/metabolism Nucleophosmin Phosphorylation Protein Binding Protein Processing, Post-Translational Protein Stability Proto-Oncogene Proteins c-akt/metabolism Proto-Oncogene Proteins c-mdm2/metabolism Serine/metabolism Tumor Suppressor Protein p53/metabolism Ultraviolet Rays
Chemicals
Biomarkers, Tumor NIBAN1 protein, human NPM1 protein, human Neoplasm Proteins Nuclear Proteins TP53 protein, human Tumor Suppressor Protein p53 Nucleophosmin Serine MDM2 protein, human Proto-Oncogene Proteins c-mdm2 Proto-Oncogene Proteins c-akt
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ji Haitao
Brain Tumor Center and Department of Neuro-Oncology, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ding Zhiyong
Hawke David
Xing Dongming
Jiang Bing-Hua
Mills Gordon B
Lu Zhimin
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-3178
DOI
10.1038/embor.2012.53
Published
2012-06-01
Epub
2012-00-01
Pages
554-60
Language
English
Region
England
NLM ID
100963049
PMCID
PMC3367238
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · 5R01CA109035 · United States
NCI NIH HHS · CA016672 · United States
NCI NIH HHS · P50 CA098258 · United States
NCI NIH HHS · R01 CA109035 · United States
NCI NIH HHS · 5 P50 CA127001-03 · United States
NCI NIH HHS · P50 CA127001 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1038/embor.2012.53 PMC Full Text View journal details
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