title: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.
abstract: Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a variety of inflammatory disease states. The protein exists as a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA. TACE is a membrane-bound disintegrin metalloproteinase. Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development. The expression of recombinant TACE (rTACE) results in the production of functional enzyme that correctly processes precursor TNF-alpha to the mature form. The rTACE provides a readily available source of enzyme to help in the search for new anti-inflammatory agents that target the final processing stage of TNF-alpha production.
authors.affiliation: Department of Molecular Biochemistry, Glaxo Wellcome Research and Development Inc., Research Triangle Park, North Carolina 27709, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Moss
authors.forename: S L
authors.initials: SL
authors.lastname: Jin
authors.forename: M E
authors.initials: ME
authors.lastname: Milla
authors.forename: D M
authors.initials: DM
authors.lastname: Bickett
authors.forename: W
authors.initials: W
authors.lastname: Burkhart
authors.forename: H L
authors.initials: HL
authors.lastname: Carter
authors.forename: W J
authors.initials: WJ
authors.lastname: Chen
authors.forename: W C
authors.initials: WC
authors.lastname: Clay
authors.forename: J R
authors.initials: JR
authors.lastname: Didsbury
authors.forename: D
authors.initials: D
authors.lastname: Hassler
authors.forename: C R
authors.initials: CR
authors.lastname: Hoffman
authors.forename: T A
authors.initials: TA
authors.lastname: Kost
authors.forename: M H
authors.initials: MH
authors.lastname: Lambert
authors.forename: M A
authors.initials: MA
authors.lastname: Leesnitzer
authors.forename: P
authors.initials: P
authors.lastname: McCauley
authors.forename: G
authors.initials: G
authors.lastname: McGeehan
authors.forename: J
authors.initials: J
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Moyer
authors.forename: G
authors.initials: G
authors.lastname: Pahel
authors.forename: W
authors.initials: W
authors.lastname: Rocque
authors.forename: L K
authors.initials: LK
authors.lastname: Overton
authors.forename: F
authors.initials: F
authors.lastname: Schoenen
authors.forename: T
authors.initials: T
authors.lastname: Seaton
authors.forename: J L
authors.initials: JL
authors.lastname: Su
authors.forename: J D
authors.initials: JD
authors.lastname: Becherer
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019483:Disintegrins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D019483:Disintegrins; D008565:Membrane Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human