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Journal article
Multiple mechanisms are implicated in the regulation of NF-kappa B activity during human cytomegalovirus infection
Proceedings of the National Academy of Sciences - PNAS, v 90(3), pp 1107-1111
01 Feb 1993
PMID: 8381532
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Abstract
Infection-induced activation of the human cytomegalovirus major immediate early enhancer/promoter has been shown to be regulated primarily by transcription factor NF-kappa B cis elements. However, the mechanism(s) by which human cytomegalovirus induces NF-kappa B activity is unknown. A study was therefore undertaken to determine how this virus would affect normal NF-kappa B regulation. Viral infection of fibroblasts resulted in the specific stimulation of promoters containing major histocompatibility complex NF-kappa B cis elements fused upstream of the chloramphenicol acetyltransferase reporter gene. Electrophoretic mobility shift assays of nuclear extracts derived from mock- and virus-infected cells showed dramatic and sustained increases in DNA-binding proteins specific for these NF-kappa B sequences. Experiments using MAD-3 I kappa B, a specific inhibitor of NF-kappa B, and antibodies directed against rel family members demonstrated that the induced binding activities contained p50 and p65 proteins but not c-rel. Northern analysis indicated maximal levels of p50 mRNA by 4 h postinfection, whereas p65 and MAD-3 I kappa B mRNA accumulation peaked at 48-72 h postinfection, suggesting different regulatory mechanisms for p50 and p65/I kappa B genes. Electrophoretic mobility shift assays with deoxycholate-treated cytoplasmic extracts demonstrated a 3- to 4-fold decrease in the cytosolic stores of NF-kappa B binding activity by 4 h postinfection. Western blots probed with antibodies directed against MAD-3 I kappa B or pp40 (a protein isolated from chicken with sequence and biochemical properties similar to those of MAD-3 I kappa B) indicated that a cross-reactive peptide of 39 kDa was no longer detectable after 24 h postinfection. These results demonstrate that the activation and maintenance of nuclear NF-kappa B DNA binding and enhancer activities upon human cytomegalovirus infection occurs by multiple mechanisms.
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Details
- Title
- Multiple mechanisms are implicated in the regulation of NF-kappa B activity during human cytomegalovirus infection
- Creators
- T F Kowalik - University of North Carolina at Chapel HillB Wing - University of North Carolina at Chapel HillJ S Haskill - University of North Carolina at Chapel HillJ C Azizkhan - University of North Carolina at Chapel HillA S Baldwin - Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill 27599-7295E S Huang - University of North Carolina at Chapel Hill
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 90(3), pp 1107-1111
- Publisher
- PNAS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:A1993KK81300069
- Scopus ID
- 2-s2.0-0027475867
- Other Identifier
- 991020200754204721
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- Web of Science research areas
- Biochemistry & Molecular Biology