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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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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



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