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A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the Nuclear Factor-κB subunit p65 in vitro and may impair Human Immunodeficiency Virus replication in these cells.
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J Exp Med - 1445.pdf | Published version | 2.02 MB | Adobe PDF | View/Open |
Title: | A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the Nuclear Factor-κB subunit p65 in vitro and may impair Human Immunodeficiency Virus replication in these cells. |
Authors: | Franzoso, G Biswas, P Poli, G Carlson, L Brown, K Tomita-Yamaguchi, M Fauci, AS Siebenlist, U |
Item Type: | Journal Article |
Abstract: | Two groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 (HIV-1) replication. "Plus" clones replicated the virus efficiently, whereas "minus" clones did not. We examined these clones for differences in nuclear factor (NF)-kappa B activity which might account for the observed phenomenon. Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools, whereas minus clones produced an apparently novel, faster-migrating complex, as judged by electrophoretic mobility shift assays. It is surprising that the faster-migrating complex was composed also of p50 and p65. However, the p65 subunit was COOH-terminally truncated, as shown by immunoprecipitation. The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases, such as elastase, cathepsin G, and proteinase 3. These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones, but not in the plus clones, as demonstrated in the case of cathepsin G. In addition, these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes, in each case correlating with the truncated from of p65. We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G. It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo-monocytic cells. The data also demonstrate that special precautions must be taken when making extracts from myelo-monocytic cells. |
Issue Date: | 1-Oct-1994 |
Date of Acceptance: | 1-Oct-1994 |
URI: | http://hdl.handle.net/10044/1/88538 |
DOI: | 10.1084/jem.180.4.1445 |
ISSN: | 0022-1007 |
Publisher: | Rockefeller University Press |
Start Page: | 1445 |
End Page: | 1456 |
Journal / Book Title: | Journal of Experimental Medicine |
Volume: | 180 |
Issue: | 4 |
Keywords: | Science & Technology Life Sciences & Biomedicine Immunology Medicine, Research & Experimental Research & Experimental Medicine HUMAN NEUTROPHIL ELASTASE HUMAN CATHEPSIN-G MONONUCLEAR PHAGOCYTES ONCOPROTEIN BCL-3 POLYMORPHONUCLEAR LEUKOCYTES TRANSCRIPTIONAL ACTIVATOR DIFFERENTIATING AGENTS MOLECULAR-CLONING LANGERHANS CELLS TYPE-1 INFECTION Animals HIV-1 Humans Monocytes NF-kappa B Rabbits Serine Endopeptidases Transcription Factor RelA Tumor Cells, Cultured Virus Replication Monocytes Tumor Cells, Cultured Animals Rabbits Humans HIV-1 Serine Endopeptidases NF-kappa B Virus Replication Transcription Factor RelA Immunology 11 Medical and Health Sciences |
Publication Status: | Published |
Online Publication Date: | 1994-10-01 |
Appears in Collections: | Department of Immunology and Inflammation |