Tgat, a Rho-specific guanine nucleotide exchange factor, activates NF-kappaB via physical association with IkappaB kinase complexes

Biochem Biophys Res Commun. 2007 Mar 30;355(1):269-74. doi: 10.1016/j.bbrc.2007.01.147. Epub 2007 Feb 2.

Abstract

Constitutive activity of NF-kappaB is associated with various human cancers including adult T-cell leukemia (ATL). In this study, we have found Tgat that activates NF-kappaB by screening a cDNA expression library derived from ATL cells. We previously identified Tgat as the oncogene, which consists of the Rho-guanine nucleotide exchange factor (Rho-GEF) domain and the unique C-terminal region, as a consequence of alternative splicing of the Trio transcript. Tgat activated the IKK activity by binding with the IkappaB kinase (IKK) complex. The Tgat mutants lacking the C-terminal region failed to associate with the IKK complex suggesting an essential role of the unique sequence. The mutation causing the loss of GEF activity also abolished the NF-kappaB activation. Moreover, co-expressed p100 was efficiently processed into p52 in the Tgat-expressing cells, suggesting the co-involvement of non-canonical pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA, Complementary / genetics
  • Genes, Reporter
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • I-kappa B Kinase / metabolism*
  • Kidney
  • Kinetics
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • DNA, Complementary
  • Guanine Nucleotide Exchange Factors
  • NF-kappa B
  • Phosphoproteins
  • Recombinant Proteins
  • Protein-Serine-Threonine Kinases
  • TRIO protein, human
  • I-kappa B Kinase