Cutting edge: TRANK, a novel cytokine that activates NF-κB and c-Jun N- terminal kinase

Valsala Haridas, Jian Ni, Anthony Meager, Jeffery Su, Guo Liang Yu, Yifan Zhai, Hla Kyaw, Keith T. Akama, Jingru Hu, Linda J. Van Eldik, Bharat B. Aggarwal

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

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-κB 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-κB and induced the degradation of the inhibitory subunit of NF-κB. In addition, TRANK upregulated the expression of NF-κB-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 flbroblasts. Its homology with antioxidant proteins, wide distribution in tissues, and ability to activate NF-κB and c-Jun N-terminal kinase suggest that TRANK plays an important role in inflammation.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Immunology
Volume161
Issue number1
StatePublished - 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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