| Lytic replication-associated protein (RAP) encoded by Kaposi sarcoma-associated herpesvirus causes p21CIP-1-mediated G1 cell cycle arrest through CCAAT/enhancer-binding protein-alpha. | |
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MedLine Citation:
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PMID: 12145325 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes Kaposi sarcoma and AIDS-related primary effusion lymphoma (PEL). Here we show that KSHV lytic cycle replication in PEL cells induces G(1) cell cycle arrest, presumably to facilitate the progression of viral DNA replication. Expression of a KSHV-encoded early lytic protein referred to as RAP or K8 is induced within 12-24 h after the onset of lytic cycle induction in host PEL cells, and coincides with increased levels of both the endogenous C/EBPalpha and p21(CIP-1) proteins in the nucleus of the same cells. The KSHV RAP protein binds to C/EBPalpha in vitro and stimulates C/EBPalpha-induced expression from both the C/EBPalpha and p21 promoters in cotransfected cells. A recombinant adenovirus expressing the RAP protein induced the expression of both the C/EBPalpha and p21 proteins in primary human fibroblasts, and flow cytometric analysis revealed a dramatic inhibition of G(1) to S cell cycle progression in the same cells. All of these effects were abolished in cells that lack C/EBPalpha or by deletion of the basic/leucine zipper region in RAP that interacts with C/EBPalpha. Therefore, C/EBPalpha is essential for the p21-mediated inhibition of G(1) to S-phase progression by RAP in KSHV-infected host cells. |
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Authors:
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Frederick Y Wu; Qi-Qun Tang; Honglin Chen; Colette ApRhys; Christopher Farrell; Jianmeng Chen; Masahiro Fujimuro; M Daniel Lane; Gary S Hayward |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2002-07-26 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 99 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-08-07 Completed Date: 2002-09-23 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 10683-8 Citation Subset: IM |
Affiliation:
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Molecular Virology Laboratories, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Adenoviruses, Human Animals Basic-Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Protein-alpha / genetics, metabolism* Carrier Proteins / genetics, metabolism* Cell Division Cell Line, Transformed Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins / genetics, metabolism* Fibroblasts / cytology G1 Phase Genetic Vectors Hela Cells Herpesvirus 8, Human / metabolism* Humans Leucine Zippers* Mice Repressor Proteins S Phase Sarcoma, Kaposi / virology Signal Transduction* Transfection Tumor Cells, Cultured Viral Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK38418/DK/NIDDK NIH HHS; DK61355/DK/NIDDK NIH HHS; R01 CA73585/CA/NCI NIH HHS; R01 CA81400/CA/NCI NIH HHS; T32 CA09243/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic-Leucine Zipper Transcription Factors; 0/CCAAT-Enhancer-Binding Protein-alpha; 0/CDKN1A protein, human; 0/Carrier Proteins; 0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/K8 protein, Human herpesvirus 8; 0/Repressor Proteins; 0/Viral Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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