Molecular cloning of the murine IL-1 beta converting enzyme cDNA.
IL-1 beta is a potent modulator of immune and inflammatory responses. Murine IL-1 beta is initially synthesized as an inactive 33-kDa pro-molecule that is activated by proteolytic cleavage between Asp-117 and Val-118 to generate the 17-kDa mature IL-1 beta protein. This cleavage is catalyzed by a specific protease that has been designated the IL-1 beta converting enzyme (or IL-1 beta convertase). We have used a human IL-1 beta convertase cDNA to isolate murine convertase cDNA from a WEHI-3 library. These cDNA predicted that the murine convertase is a 402-residue protein. Overall, the murine convertase showed 71% nucleotide and 62% predicted amino acid sequence identity with the human convertase. Southern blot analysis of interspecific backcross mice indicated that the murine IL-1 beta convertase is encoded by a single copy gene located on murine chromosome 9. The murine convertase showed broad constitutive expression, being detected in mononuclear phagocyte and T lymphocyte cell lines as well as in spleen, heart, brain, and adrenal glands. The expression of the murine convertase in mononuclear phagocytes was up-regulated by treatment with LPS or rIFN-gamma. These studies establish that the IL-1 beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level.
Nett
M A
MA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Cerretti
D P
DP
Berson
D R
DR
Seavitt
J
J
Gilbert
D J
DJ
Jenkins
N A
NA
Copeland
N G
NG
Black
R A
RA
Chaplin
D D
DD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D010450:Endopeptidases / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D010450:Endopeptidases