Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1

Sunil K. Manna, Banaganapalli Babajan, Pongali B. Raghavendra, Nune Raviprakash, Chitta Sureshkumar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4- thiadiazolidine (P3-25) is known to possess anti-bacterial, anti-fungal, and anti-tubercular activities. In this report, we provide evidence that P3-25 inhibits NF-κB, known to induce inflammatory and tumorigenic responses. It activates. AP-1, another transcription factor. It inhibits TRAF2-mediated NF-κB activation but not TRAF6-mediated NF-κB DNA binding by preventing its association with TANK (TRAF for NF-κB). It facilitates binding of MEKK1 with TRAF2 and thereby activates JNK and AP-1.Weprovide evidence, for the first time, that suggests that the interaction of P3-25 with TRAF2 leads to inhibition of the NF-κB pathway and activation of AP-1 pathway. These results suggest novel approaches to design of P3-25 as an anti-cancer/inflammatory drug for therapy through regulation of the TRAF2 pathway.

Original languageEnglish
Pages (from-to)11617-11627
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number15
DOIs
Publication statusPublished - 09-04-2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Manna, S. K., Babajan, B., Raghavendra, P. B., Raviprakash, N., & Sureshkumar, C. (2010). Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1. Journal of Biological Chemistry, 285(15), 11617-11627. https://doi.org/10.1074/jbc.M109.094961