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CUTTING EDGE |
B and c-Jun N-Terminal Kinase1
*
Cytokine Research Section, Department of Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Human Genome Sciences, Inc., Rockville, MD 20850;
Division of Immunobiology, The National Institute for Biological Standards and Control, South Mimms, U.K.; and
§
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
We searched the expressed sequence tag database using
sequence homology and identified a novel cytokine, which we have named
TRANK (thioredoxin peroxidase-related activator of NF-
B and c-Jun
N-terminal kinase). The predicted amino acid sequence of TRANK was
highly homologous to that of the thiol-specific antioxidant proteins.
Unlike these proteins, however, TRANK had a putative secretory signal
polypeptide and was found to be secreted by cells. TRANK was expressed
in most tissues and cell lines, and the gene that encodes it was mapped
to chromosome Xp21–22.1. TRANK activated NF-B and induced the
degradation of the inhibitory subunit of NF-B. In addition, TRANK
up-regulated the expression of NF-B-dependent gene products, ICAM-1,
and inducible nitric oxide synthase. TRANK also activated c-Jun
N-terminal kinase and induced the proliferation of normal human
foreskin fibroblasts. Its homology with antioxidant proteins, wide
distribution in tissues, and ability to activate NF-B and c-Jun
N-terminal kinase suggest that TRANK plays an important role in
inflammation.
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