κB-Ras is a nuclear-cytoplasmic small GTpase that inhibits NF-κB activation through the suppression of transcriptional activation of p65/RelA

Kenji Tago, Megumi Funakoshi-Tago, Masaki Sakinawa, Norikazu Mizuno, Hiroshi Itoh

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

NF-κB is an important transcription factor involved in various biological responses, including inflammation, cell differentiation, and tumorigenesis. κB-Ras was identified as an IκB-interacting small GTPase and is reported to disturb cytokine-induced NF-κB activation. In this study, we established that κB-Ras is a novel type of nuclear-cytoplasmic small GTPase that mainly binds to GTP, and its localization seemed to be regulated by its GTP/GDP-binding state. Unexpectedly, the GDP-binding form of the κB-Ras mutant exhibited a more potent inhibitory effect on NF-κB activation, and this inhibitory effect seemed to be due to suppression of the transactivation of a p65/RelA NF-κB subunit. κB-Ras suppressed phosphorylation at serine 276 on the p65/RelA subunit, resulting in decreased interaction between p65/RelA and the transcriptional coactivator p300. Interestingly, the GDP-bound κB-Ras mutant exhibited higher interactive affinity with p65/RelA and inhibited the phosphorylation of p65/RelA more potently than wild-type κB-Ras. Taken together, these findings suggest that the GDP-bound form of κB-Ras in cytoplasm suppresses NF-κB activation by inhibiting its transcriptional activation.

Original languageEnglish
Pages (from-to)30622-30633
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number40
DOIs
Publication statusPublished - 2010 Oct 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'κB-Ras is a nuclear-cytoplasmic small GTpase that inhibits NF-κB activation through the suppression of transcriptional activation of p65/RelA'. Together they form a unique fingerprint.

Cite this