Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 8, Pages 2647-2652Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806677106
Keywords
NF-kappaB; nuclear transport; transcription; molecular motor; active transport
Categories
Funding
- Sontag Foundation Distinguished Scientist Award
- Alfred P. Sloan Foundation Fellowship
- Braude Foundation
- NIH [RO1MH080740]
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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-kappa B) family. The p65: p50 NF-kappa B heterodimer that predominates in many cell types can undergo stimulated movement, following degradation of the I kappa B inhibitor, as well as shuttling in the absence of stimulation with I kappa B 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-kappa B. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-kappa B 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-kappa B-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-kappa B may be a conserved mechanism in the NF-kappa B activation pathway and could represent a potential point of regulation.
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