Inhibiting TRAF2-mediated activation of NF-kappaB facilitates induction of AP-1.

The Journal of Biological Chemistry
Sunil K MannaChitta Sureshkumar

Abstract

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

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Citations

Dec 4, 2010·The Journal of Biological Chemistry·Maikho ThohSunil K Manna
Dec 16, 2010·The Journal of Biological Chemistry·Sunil K MannaMaikho Thoh
May 17, 2011·PloS One·Usha S NaikSunil K Manna
Dec 8, 2015·BMC Complementary and Alternative Medicine·Looi Ting YeongNorhafizah Mohtarrudin
Jun 14, 2013·Journal of Molecular Signaling·Ping Xie
Mar 20, 2016·Biochemical Pharmacology·Alice BorghiRudi Beyaert
Jun 22, 2016·Apoptosis : an International Journal on Programmed Cell Death·Raveendra B MokhamatamSunil K Manna
Dec 16, 2011·Oncotarget·Luca D'Agostino, Antonio Giordano
Nov 1, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Tushar S Basu BaulM Fátima C Guedes da Silva
Jan 21, 2016·The Biochemical Journal·Adeel H Zaidi, Sunil K Manna

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