Modulation of NF-κB activity by exchange of dimers

Simona Saccani, Serafino Pantano, Gioacchino Natoli

Research output: Contribution to journalArticle

Abstract

Transcription factors within a family usually share the ability to recognize similar or identical consensus sites. For example, the five mammalian NF-κB/Rel proteins generate more than 12 dimers recognizing 9-11 nucleotide κB sites. Each dimer selectively regulates a few target promoters; however, several genes are redundantly induced by more than one dimer. Whether this property simply generates redundancy in target gene activation or underlies more complex regulatory mechanisms is an open issue. We show here that during dendritic cell maturation, rapidly activated dimers (e.g., p50/RelA) bound to a subset of target promoters are gradually replaced by slowly activated dimers (e.g., p52/RelB). Since the dimers have different transcriptional activity at each promoter, the dimer exchange allows fine tuning of the response over time. Further, due to the insensitivity of p52/RelB to the NF-κB inhibitors, the IκBs, dimer exchange contributes to sustained activation of selected NF-κB targets in spite of the resynthesis of IκBα.

Original languageEnglish
Pages (from-to)1563-1574
Number of pages12
JournalMolecular Cell
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

ASJC Scopus subject areas

  • Molecular Biology

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