A nonsecretable cell surface mutant of tumor necrosis factor (TNF) kills by cell-to-cell contact. NLM AIDSLINE Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

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A nonsecretable cell surface mutant of tumor necrosis factor (TNF) kills by cell-to-cell contact.

Cell. 1990 Oct 19;63(2):251-8. Unique Identifier : AIDSLINE MED/91004233
Perez C; Albert I; DeFay K; Zachariades N; Gooding L; Kriegler M; Department of Molecular Biology, Cetus Corporation, Emeryville,; California 94608.

Abstract: In addition to the induction of tumor regression, tumor necrosis factor (TNF) has been implicated as the causative agent in a number of pathologies, including cachexia, septic shock, rheumatoid arthritis, autoimmunity, and induction of HIV expression. We propose that this complex physiology might be manifest by different forms of TNF: the 17 kd secretory component, the 26 kd transmembrane form, or both. To determine whether the 26 kd form of TNF was biologically active and whether its biology differed from that of the secretory component, we generated uncleavable and solely secretable mutants of TNF and studied their biological activities. We found that an uncleavable mutant of the 26 kd cell surface transmembrane form of TNF kills tumor cells and virus-infected cells by cell-to-cell contact, and that TNF need not be internalized by its target to kill. Thus, the 26 kd integral transmembrane form of TNF may function in vivo to kill tumor cells and other targets locally in contrast to the systemic bioactivity of the secretory component.
Keywords: Amino Acid Sequence Animal Cell Communication/*DRUG EFFECTS Cell Line Cell Survival/*DRUG EFFECTS Cell Transformation, Viral Mice Molecular Sequence Data Molecular Weight *Mutagenesis, Site-Directed Oligonucleotide Probes Phenotype Plasmids Recombinant Proteins/PHARMACOLOGY Restriction Mapping Support, U.S. Gov't, P.H.S. Transfection Tumor Necrosis Factor/*GENETICS/PHARMACOLOGY JOURNAL ARTICLEKWDaminoacidsequenceanimalcellcommunication/KWDdrugeffectscelllinecellsurvival/KWDdrugeffectscelltransformation,viralmicemolecularsequencedatamolecularweightKWDmutagenesis,site-directedoligonucleotideprobesphenotypeplasmidsrecombinantproteins/pharmacologyrestrictionmappingsupport,uKWDsKWDgov't,pKWDhKWDsKWDtransfectiontumornecrosisfactor/KWDgenetics/pharmacologyjournalarticle
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Copyright © 1991 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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