Document Detail


K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis.
MedLine Citation:
PMID:  17090655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of the K1 gene of human herpesvirus 8 activates nuclear factor-kappaB and induces lymph node hyperplasia and lymphomas in transgenic mice. To further delineate its role in cell survival, we determined whether K1 altered apoptosis of lymphoma cells. K1 protein is expressed in Kaposi sarcoma and primary effusion lymphoma. We retrovirally transfected BJAB lymphoma, THP-1, U937, and Kaposi sarcoma SLK cells to express K1 and a K1 mutant with the deleted immunoreceptor tyrosine-based activation motif (K1m). We challenged cells with an agonistic anti-Fas antibody, Fas ligand, irradiation, and tumor necrosis factor-related apoptosis-inducing ligand. K1 transfectants but not K1m transfectants exhibited reduced levels of apoptosis induced by the anti-Fas antibody but not apoptosis induced by the tumor necrosis factor-related apoptosis-inducing ligand or irradiation. K1 expression resulted in reduced apoptosis rates as shown in several assays. K1 induced a modest reduction in levels of Fas-associated death domain protein, and procaspase 8 recruited to the death-inducing signaling complex. Finally, K1 transfectants cleaved procaspase 8 at significantly lower rates than did K1m transfectants. K1-transfected mice, compared with vector-transfected mice, showed lower death rates after challenge with anti-Fas antibody. K1 may contribute to lymphoma development by stimulating cell survival by selectively blocking Fas-mediated apoptosis.
Authors:
Suizhao Wang; Shu Wang; Hoyoung Maeng; Daniel P Young; Om Prakash; Luis E Fayad; Anas Younes; Felipe Samaniego
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-07
Journal Detail:
Title:  Blood     Volume:  109     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-21     Completed Date:  2007-03-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2174-82     Citation Subset:  AIM; IM    
Affiliation:
Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / immunology
Antigens, CD95 / immunology,  metabolism*
Apoptosis*
Cell Line, Tumor
Gene Expression
Humans
Lymphoma / genetics,  metabolism*,  pathology*
Plasmids / genetics
Survival Rate
Transfection
Viral Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
CA098412/CA/NCI NIH HHS; CA106173/CA/NCI NIH HHS; CA16672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD95; 0/K1 protein, Human herpesvirus 8; 0/Viral Proteins
Comments/Corrections

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