Stimulated Nuclear Translocation of NF-kappaB and Shuttling Differentially Depend on Dynein and the Dynactin Complex

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Feb 7

PMID 19196984

Citations 49

Authors

Cynthia K Shrum

Daniel DeFrancisco

Mollie K Meffert

Affiliations

Soon will be listed here.

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-kappaB) family. The p65:p50 NF-kappaB heterodimer that predominates in many cell types can undergo stimulated movement, following degradation of the IkappaB inhibitor, as well as shuttling in the absence of stimulation with IkappaB 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-kappaB. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-kappaB 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-kappaB-dependent gene expression showed a dependence on endogenous dynein in a variety of cell types and in response to diverse activating stimuli, suggesting that dynein-dependent transport of NF-kappaB may be a conserved mechanism in the NF-kappaB activation pathway and could represent a potential point of regulation.

Citing Articles

Anti-Inflammatory and Cancer-Preventive Potential of Chamomile ( L.): A Comprehensive In Silico and In Vitro Study.

Drif A, Yucer R, Damiescu R, Ali N, Abu Hagar T, Avula B Biomedicines. 2024; 12(7).

PMID: 39062057 PMC: 11275008. DOI: 10.3390/biomedicines12071484.

Kinetochore-fiber lengths are maintained locally but coordinated globally by poles in the mammalian spindle.

Richter M, Neahring L, Tao J, Sutanto R, Cho N, Dumont S Elife. 2023; 12.

PMID: 37395732 PMC: 10348741. DOI: 10.7554/eLife.85208.

Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α.

Wang N, Lu Y, Rothrauff B, Zheng A, Lamb A, Yan Y Bone Res. 2023; 11(1):13.

PMID: 36869045 PMC: 9984452. DOI: 10.1038/s41413-023-00248-x.

LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus.

Wu Z, Berlemann L, Bader V, Sehr D, Dawin E, Covallero A EMBO J. 2022; 41(24):e112006.

PMID: 36398858 PMC: 9753471. DOI: 10.15252/embj.2022112006.

The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.

Verzella D, Cornice J, Arboretto P, Vecchiotti D, Di Vito Nolfi M, Capece D Biomedicines. 2022; 10(9).

PMID: 36140335 PMC: 9496094. DOI: 10.3390/biomedicines10092233.

References

Ross J, Wallace K, Shuman H, Goldman Y, Holzbaur E . Processive bidirectional motion of dynein-dynactin complexes in vitro. Nat Cell Biol. 2006; 8(6):562-70. DOI: 10.1038/ncb1421. View

Rosette C, Karin M . Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-kappa B. J Cell Biol. 1995; 128(6):1111-9. PMC: 2120413. DOI: 10.1083/jcb.128.6.1111. View

King S, Schroer T . Dynactin increases the processivity of the cytoplasmic dynein motor. Nat Cell Biol. 2000; 2(1):20-4. DOI: 10.1038/71338. View

Pomerantz J, Denny E, Baltimore D . CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. EMBO J. 2002; 21(19):5184-94. PMC: 129028. DOI: 10.1093/emboj/cdf505. View

Lois C, Hong E, Pease S, Brown E, Baltimore D . Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 2002; 295(5556):868-72. DOI: 10.1126/science.1067081. View

Suzuki M, Igarashi R, Sekiya M, Utsugi T, Morishita S, Yukawa M . Dynactin is involved in a checkpoint to monitor cell wall synthesis in Saccharomyces cerevisiae. Nat Cell Biol. 2004; 6(9):861-71. DOI: 10.1038/ncb1162. View

Giannakakou P, Sackett D, Ward Y, Webster K, Blagosklonny M, Fojo T . p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nat Cell Biol. 2000; 2(10):709-17. DOI: 10.1038/35036335. View

Herman A, Croteau G, Sekaly R, Kappler J, Marrack P . HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J Exp Med. 1990; 172(3):709-17. PMC: 2188560. DOI: 10.1084/jem.172.3.709. View

Combs J, Kim S, Tan S, Ligon L, Holzbaur E, Kuhn J . Recruitment of dynein to the Jurkat immunological synapse. Proc Natl Acad Sci U S A. 2006; 103(40):14883-8. PMC: 1595445. DOI: 10.1073/pnas.0600914103. View

10.

Cheung P, Zhang Y, Long J, Lin S, Zhang M, Jiang Y . p150(Glued), Dynein, and microtubules are specifically required for activation of MKK3/6 and p38 MAPKs. J Biol Chem. 2004; 279(44):45308-11. DOI: 10.1074/jbc.C400333200. View

11.

Meffert M, Chang J, Wiltgen B, Fanselow M, Baltimore D . NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci. 2003; 6(10):1072-8. DOI: 10.1038/nn1110. View

12.

Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C . TNF-alpha mediated transport of NF-kappaB to the nucleus is independent of the cytoskeleton-based transport system in non-neuronal cells. Eur J Cell Biol. 2006; 85(6):529-36. DOI: 10.1016/j.ejcb.2006.02.007. View

13.

Fagerlund R, Kinnunen L, Kohler M, Julkunen I, Melen K . NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4. J Biol Chem. 2005; 280(16):15942-51. DOI: 10.1074/jbc.M500814200. View

14.

Spencer W, Kwon H, Crepieux P, Leclerc N, Lin R, Hiscott J . Taxol selectively blocks microtubule dependent NF-kappaB activation by phorbol ester via inhibition of IkappaBalpha phosphorylation and degradation. Oncogene. 1999; 18(2):495-505. DOI: 10.1038/sj.onc.1202335. View

15.

Mackenzie G, Oteiza P . Zinc and the cytoskeleton in the neuronal modulation of transcription factor NFAT. J Cell Physiol. 2006; 210(1):246-56. DOI: 10.1002/jcp.20861. View

16.

Wiegert J, Bengtson C, Bading H . Diffusion and not active transport underlies and limits ERK1/2 synapse-to-nucleus signaling in hippocampal neurons. J Biol Chem. 2007; 282(40):29621-33. DOI: 10.1074/jbc.M701448200. View

17.

Cheng H, Liu S, Lee H, Lin Y, Huang Z, Hsu C . Heavy chain of cytoplasmic dynein is a major component of the postsynaptic density fraction. J Neurosci Res. 2006; 84(2):244-54. DOI: 10.1002/jnr.20898. View

18.

Mesika A, Kiss V, Brumfeld V, Ghosh G, Reich Z . Enhanced intracellular mobility and nuclear accumulation of DNA plasmids associated with a karyophilic protein. Hum Gene Ther. 2005; 16(2):200-8. DOI: 10.1089/hum.2005.16.200. View

19.

Kim H, Ling S, Rogers G, Kural C, Selvin P, Rogers S . Microtubule binding by dynactin is required for microtubule organization but not cargo transport. J Cell Biol. 2007; 176(5):641-51. PMC: 2064022. DOI: 10.1083/jcb.200608128. View

20.

Jin T, Li J . Dynamitin controls Beta 2 integrin avidity by modulating cytoskeletal constraint on integrin molecules. J Biol Chem. 2002; 277(36):32963-9. DOI: 10.1074/jbc.M201525200. View