Document Detail

Bcl-X(L) is the primary mediator of p21 protection against hyperoxia-induced cell death.
MedLine Citation:
PMID:  21128858     Owner:  NLM     Status:  MEDLINE    
A tight balance between anti- and proapoptotic members of the Bcl-2 family controls cell survival and death. Exposure to hyperoxia shifts this balance towards a prodeath state that ultimately activates Bak- and Bax-dependent cell death. Mechanisms underlying this shift are undefined; however, the cell cycle inhibitor p21 delays the loss of antiapoptotic Mcl-1 and Bcl-X(L), and protects against hyperoxia. Here, H1299 human lung adenocarcinoma cells are used to investigate how these and other members of the Bcl-2 family cooperate with p21 to protect against hyperoxia. Expression of antiapoptotic Mcl-1 and Bcl-X(L), but not Bcl-2 or A1, declined during hyperoxia, whereas proapoptotic Bak, but not Bax, increased. Conditional overexpression of p21 selectively delayed the loss of Mcl-1 and Bcl-X(L), without affecting expression of the other members. siRNA knockdown of Mcl-1 and Bcl-X(L) sensitized cells to hyperoxia, but only the loss of Bcl-X(L) ablated the protective effects of p21. Conversely, overexpression of Mcl-1 and Bcl-X(L) protected against hyperoxia, but only Bcl-X(L) bound Bak and Bax. Altogether, these data suggest that Bcl-X(L) is the primary mediator by which p21 protects against hyperoxia-induced Bak/Bax-dependent cell death.
Yu-Chieh M Wu; Michael A O'Reilly
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-04
Journal Detail:
Title:  Experimental lung research     Volume:  37     ISSN:  1521-0499     ISO Abbreviation:  Exp. Lung Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-18     Completed Date:  2011-06-09     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  8004944     Medline TA:  Exp Lung Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  82-91     Citation Subset:  IM    
Department of Biomedical Genetics, School of Medicine and Dentistry, The University of Rochester, Rochester, New York 14642, USA.
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MeSH Terms
Adenocarcinoma / metabolism,  pathology
Apoptosis / drug effects,  physiology*
Cell Death / drug effects,  physiology
Cell Line, Tumor
Cell Survival / drug effects,  physiology
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism,  physiology*
Lung Neoplasms / metabolism,  pathology
Oxygen / administration & dosage*
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism
RNA, Small Interfering / genetics
bcl-2 Homologous Antagonist-Killer Protein / metabolism
bcl-2-Associated X Protein / metabolism
bcl-X Protein / genetics,  metabolism,  physiology*
Grant Support
Reg. No./Substance:
0/BAK1 protein, human; 0/BAX protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 0/myeloid cell leukemia sequence 1 protein; 7782-44-7/Oxygen

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