NF-κB is essential for induction of CYLD, the negative regulator of NF-κB: Evidence for a novel inducible autoregulatory feedback pathway

Hirofumi Jono, Jae Hyang Lim, Lin Feng Chen, Haidong Xu, Eirini Trompouki, Zhixing K. Pan, George Mosialos, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

The transcription factor NF-κ regulates genes involved in inflammatory and immune responses, tumorigenesis, and apoptosis. In contrast to the pleiotropic stimuli that lead to its positive regulation, the known signaling mechanisms that underlie the negative regulation of NF-κ are very few. Recent studies have identified the tumor suppressor CYLD, loss of which causes a benign human syndrome called cylindromatosis, as a key negative regulator for NF-κ signaling by deubiquitinating tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2, TBAF6, and NEMO (NF-κ essential modulator, also known as IκB kinase γ). However, how CYLD is regulated remains unknown. The present study revealed a novel autoregulatory feedback pathway through which activation of NF-κB by TNF-α and bacterium nontypeable Haemophilus influenzae (NTHi) induces CYLD that in turn leads to the negative regulation of NF-κB signaling. In addition, TRAF2 and TBAF6 appear to be differentially involved in NF-κB-dependent induction of CYLD by TNF-á and NTH-κB. These findings provide novel insights into the autoregulation of NF-κB activation.

Original languageEnglish
Pages (from-to)36171-36174
Number of pages4
JournalJournal of Biological Chemistry
Volume279
Issue number35
DOIs
StatePublished - 27 Aug 2004

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