Document Detail


Regulation of Actinomycin D induced upregulation of Mdm2 in H1299 cells.
MedLine Citation:
PMID:  22051195     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mdm2 is a critical negative regulator of the p53 tumor suppressor and also has many p53-independent functions. Deregulation of Mdm2 is closely associated with tumorigenesis. However, how Mdm2 is regulated in response to various stresses is not well understood. In this study, we found that Mdm2 was stabilized and upregulated upon Actinomycin D (ActD) treatment in the p53-deficient H1299 cell line. This Mdm2 upregulation was not dependent on the ribosomal protein L11, an essential player in ribosomal stress-induced p53 activation, but did require a NEDDylation-dependent mechanism. We further demonstrated that the ActD-induced Mdm2 stabilization may be modulated by the cell growth signaling, and that knockdown of Mdm2 enhanced ActD-induced cell death in H1299 cells. These results suggested a role of Mdm2 in the ribosomal stress response in the p53 deficient cells, which could be exploited in therapeutic use for treating cancers harboring p53 mutations.
Authors:
Lianjie Li; Di Cui; Shijun J Zheng; Huiqiang Lou; Jun Tang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-1
Journal Detail:
Title:  DNA repair     Volume:  -     ISSN:  1568-7856     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
State Key Laboratory of Agrobiotechnology, China Agricultural University, 2 Yuan-Ming-Yuan West Road, Beijing 100193, PR China; College of Veterinary Medicine, China Agricultural University, 2 Yuan-Ming-Yuan West Road, Beijing 100193, PR China.
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