Document Detail


EDAG interact with NPM1 (Nucleophosmin/B23) and increases its protein stability, resisting cell apoptosis.
MedLine Citation:
PMID:  22712502     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
EDAG is a hematopoietic tissue-specific transcription regulator that plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. In AML patients, the high expression level of EDAG is associated with poor prognosis. NPM1 (Nucleophosmin or B23), a ubiquitous nucleolar phosphoprotein, has been proved to be a multifunctional protein that is involved in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth, and transformation. Various studies have implicated NPM1 overexpression in promoting tumor cell proliferation, blocking differentiation of leukemia cells and resisting apoptosis. In the present study, using co-immunoprecipitation, we characterized EDAG as a physiological binding partner of NPM1; The N-terminal (1-124aa) region of EDAG interacts with the N-terminal (118-187aa) of NPM1. Under CHX treatment, the stability of NPM1 protein was enhanced by EDAG overexpression, while knockdown of EDAG by lentivirus-mediated siRNA resulted in an increased degradation rate of NPM1 in K562 cells. During PMA-induced K562 megakaryocytic differentiation, overexpression of EDAG prevented the down-regulation of NPM1 proteins, while knockdown of EDAG accelerated the down-regulation of NPM1. EDAG deletion mutant lacking the binding domain with NPM1 lost the ability to stabilize NPM1 protein. Furthermore, knockdown of EDAG in K562 cells led to increased cell apoptosis induced by imatinib, and re-expression of NPM1 attenuated the increased apoptosis. These results suggest that EDAG enhances the protein stability of NPM1 through binding to NPM1, which plays a critical role in the anti-apoptosis of leukemia cells.
Authors:
Mei-Jiang Zhang; Ya-Li Ding; Cheng-Wang Xu; Yang Yang; Wen-Xi Lian; Yi-Qun Zhan; Wei Li; Wang-Xiang Xu; Miao Yu; Chang-Hui Ge; Hong-Mei Ning; Chang-Yan Li; Xiao-Ming Yang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-19
Journal Detail:
Title:  The FEBS journal     Volume:  -     ISSN:  1742-4658     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal compilation © 2012 Federation of European Biochemical Societies.
Affiliation:
Tianjin University, Department of pharmaceutical engineering, Tianjin China, 300072 Beijing Institute of Radiation Medicine, Beijing, China, 100850 State Key laboratory of Proteomics, Beijing, China, 100850 Purdue University, Department of Biological Sciences, 915 W. State Street West Lafayette, IN 47907-2054 Anhui Medical University, Hefei, China, 230032 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing, China, 100071.
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