Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-κB pathway

Biochem Biophys Res Commun. 2010 Oct 1;400(4):581-6. doi: 10.1016/j.bbrc.2010.08.107. Epub 2010 Sep 6.

Abstract

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its function is mediated through lymphotoxin-β receptor (LTβR), which is known to play important roles in inflammatory and immune responses through activation of NF-κB signaling pathways. However, molecular mechanism of LTβR ligation-induced NF-κB signaling remains incompletely understood. In this report we demonstrate that a novel zinc-finger protein 91 (ZFP91) is a critical regulator in LIGHT-induced activation of non-canonical NF-κB pathway. ZFP91 appears to be required for NF-κB2 (p100) processing to p52, nuclear translocation of p52 and RelB, and DNA-binding activity of NF-κB in LIGHT-induced activation of non-canonical NF-κB pathway. Furthermore, ZFP91 knock-down by RNA interference blocks the LIGHT-induced accumulation of NIK and p100 processing, as well as the expression of non-canonical NF-κB target genes. These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-κB pathway in LTβR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Ligand / metabolism
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Lymphotoxin beta Receptor / metabolism
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Transcription Factor RelA / metabolism
  • Transcription Factor RelB / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology*

Substances

  • Lymphotoxin beta Receptor
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • RELB protein, human
  • RNA, Small Interfering
  • TNFSF14 protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • CD40 Ligand
  • Transcription Factor RelB
  • Ubiquitin-Protein Ligases
  • ZFP91 protein, human