SMN1 functions as a novel inhibitor for TRAF6-mediated NF-κB signaling

Eun Kyung Kim, Eui Ju Choi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Survival motor neuron (SMN) is a 38-kDa protein, whose deficiency in humans develops spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disease with muscular atrophy due to motor neuron death in the spinal cord. We now report that SMN prevents the activation of TRAF6 and IκB kinase (IKK) and thereby negatively regulates the NF-κB signaling processes. SMN physically interacted with TRAF6 and with each component of the IKK complex, IKK-α, IKK-β, and IKK-γ in BV2 microglia cells. Moreover, SMN1 inhibited the E3 ubiquitin ligase activity of TRAF6 as well as the kinase activity of IKK. Furthermore, depletion of endogenous SMN by RNA interference enhanced the IL-1β-induced activation of IKK and production of inflammatory mediators such as TNF-α and nitric oxide in BV2 cells. Consistently, the potentiation of IL-1β-induced IKK activity was also found in SMA patient fibroblasts, compared with that of normal ones. Our results thus suggest that SMN functions as a natural inhibitor for IL-1β-induced NF-κB signaling by targeting TRAF6 and the IKK complex.

Original languageEnglish
Pages (from-to)760-770
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1864
Issue number5
DOIs
Publication statusPublished - 2017 May 1

Fingerprint

TNF Receptor-Associated Factor 6
Motor Neurons
Interleukin-1
Spinal Muscular Atrophy
Phosphotransferases
Protein Deficiency
Ubiquitin-Protein Ligases
Muscular Atrophy
Microglia
RNA Interference
Neurodegenerative Diseases
Spinal Cord
Nitric Oxide
Fibroblasts

Keywords

  • NF-κB signaling
  • Spinal muscular atrophy
  • Survival motor neuron
  • TRAF6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

SMN1 functions as a novel inhibitor for TRAF6-mediated NF-κB signaling. / Kim, Eun Kyung; Choi, Eui Ju.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1864, No. 5, 01.05.2017, p. 760-770.

Research output: Contribution to journalArticle

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