Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex

Cynthia K. Shrum, Daniel Defrancisco, Mollie K. Meffert

Research output: Contribution to journalArticle

Abstract

Translocation from the cytoplasm to the nucleus is required for the regulation of gene expression by transcription factors of the nuclear factor kappa B (NF-κB) family. The p65:p50 NF-κB heterodimer that predominates in many cell types can undergo stimulated movement, following degradation of the IκB inhibitor, as well as shuttling in the absence of stimulation with IκB bound. Disruption of the dynactin complex and knockdown of endogenous dynein were used to investigate the nuclear translocation requirements for stimulated and shuttling movement of NF-κB. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-κB used active dynein-dependent transport following stimulation while translocation during shuttling was mediated by a dynein-independent pathway that could be potentiated by dynactin disruption, consistent with a process of facilitated diffusion. Nuclear translocation and activation of NF-κB-dependent gene expression showed a dependence on endogenous dynein in a variety of cell types and in response to diverse activating stimuli, suggesting that dyneindependent transport of NF-κB may be a conserved mechanism in the NF-κB activation pathway and could represent a potential point of regulation.

Original languageEnglish (US)
Pages (from-to)2647-2652
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number8
DOIs
StatePublished - Feb 24 2009

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Keywords

  • Molecular motor active transport
  • NF-kappaB
  • Nuclear transport
  • Transcription

ASJC Scopus subject areas

  • General

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