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

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TNF Receptor-Associated Factor 2
Transcription Factor AP-1
Chemical activation
TNF Receptor-Associated Factor 6
Anti-Inflammatory Agents
Transcription Factors
Association reactions
Drug Therapy
DNA
Pharmaceutical Preparations
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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
Manna, Sunil K. ; Babajan, Banaganapalli ; Raghavendra, Pongali B. ; Raviprakash, Nune ; Sureshkumar, Chitta. / Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 15. pp. 11617-11627.
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Manna, SK, Babajan, B, Raghavendra, PB, Raviprakash, N & Sureshkumar, C 2010, 'Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1', Journal of Biological Chemistry, vol. 285, no. 15, pp. 11617-11627. https://doi.org/10.1074/jbc.M109.094961

Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1. / Manna, Sunil K.; Babajan, Banaganapalli; Raghavendra, Pongali B.; Raviprakash, Nune; Sureshkumar, Chitta.

In: Journal of Biological Chemistry, Vol. 285, No. 15, 09.04.2010, p. 11617-11627.

Research output: Contribution to journalArticle

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Manna SK, Babajan B, Raghavendra PB, Raviprakash N, Sureshkumar C. Inhibiting TRAF2-mediated activation of NF-κB facilitates induction of AP-1. Journal of Biological Chemistry. 2010 Apr 9;285(15):11617-11627. https://doi.org/10.1074/jbc.M109.094961