Partial purification and characterization of a tumor necrosis factor-alpha converting activity

European Journal of Immunology
S Robache-GalleaS Roman-Roman

Abstract

Tumor necrosis factor (TNF)-alpha is initially synthesized as an extracellular membrane-associated 26-kDa protein that is further cleaved at Ala76-Val77 to yield the soluble 17-kDa form. Recently, peptide-hydroxamate metalloproteinase inhibitors have been reported to block the proteolytic processing of TNF-alpha, thus suggesting that the putative TNF-alpha converting enzyme (TACE) is a zinc-dependent metalloendopeptidase. In this report, we characterize a TNF-alpha converting activity (TACA) that cleaves in vitro the human 26-kDa TNF-alpha at the physiological processing site. The chromatography steps followed for purification and the use of a panel of proteinase inhibitors indicate that the enzyme responsible for TACA is a membrane glycosylated metalloendopeptidase which is most likely different from the matrix-degrading metalloproteinases. The failure of TACA to process a Val77-->Gly77 precursor mutant emphasizes the importance of hydrophobic residue at P1' position. In addition, TACA is not able to cleave the mouse pro-TNF-alpha and does not catalyze in vitro the processing of other transmembrane proteins susceptible to metalloproteinase-mediated shedding, such as interleukin-6 or TNF receptors. These studies suggest the exi...Continue Reading

References

Jan 1, 1992·Annual Review of Immunology·P Vassalli
May 1, 1991·Immunology Today·S ChouaibW A Buurman
May 26, 1983·Biochimica Et Biophysica Acta·T MaedaS Q Mehdi
Dec 1, 1995·The Journal of Experimental Medicine·N KayagakiH Yagita
Aug 1, 1995·European Journal of Immunology·S M MarianiP H Krammer
Jun 1, 1995·Current Biology : CB·C A Dinarello, N H Margolis
Oct 6, 1995·The Journal of Biological Chemistry·S Robache-GalleaS Roman-Roman
May 1, 1995·Journal of Leukocyte Biology·A J GearingR Gilbert
Jan 1, 1994·Annual Review of Medicine·K J Tracey, A Cerami
Jan 1, 1993·Annual Review of Biochemistry·J Massagué, A Pandiella
May 17, 1996·The Journal of Biological Chemistry·G PreeceA Ager

❮ Previous
Next ❯

Citations

Apr 14, 2010·The Journal of Biological Chemistry·Sharron A N BrownJeffrey A Winkles
Aug 22, 2001·In Vitro Cellular & Developmental Biology. Animal·Y D TchoukalovaG J Hausman
Oct 2, 1998·FEBS Letters·A AmourG Murphy
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·C WatanabeH Kikutani

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.