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PMID: 14668491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rac GTPase instructs nuclear factor-kappaB activation by conveying the SCF complex and IkBalpha to the ruffling membranes.

Molecular biology of the cell ·Vol. 15 ·No. 3 ·2004-03-00 ·Pages 1124-33

Boyer L, Travaglione S, Falzano L, Gauthier NC, Popoff MR, Lemichez E, Fiorentini C, Fabbri A

Abstract

Nuclear factor-kappaB (NF-kappaB) is a ubiquitously expressed transcription factor that plays a central role in directing a vast range of cellular functions. Its activation is controlled by the Rac GTPase and relies on the coordinated cooperation of the E3-ligase complex SCF(betaTrCP), composed by Skp-1/Cullin-1, Rbx/Roc1, and the beta-TrCP proteins. Recently, Cullin-1 has been reported to form a complex with the activated Rac GTPase. Here, we show that the specific activation of the Rac GTPase, besides directing its own positioning, induces the relocalization of the SCF component Cullin-1 to the ruffling membranes. This occurred only if the ruffles were stimulated by the Rac GTPase and was accompanied by the repositioning to the same intracellular compartment of the SCF protein Skp-1 and the ubiquitin-like molecule Nedd-8. The SCF substrate IkBalpha was also directed to the ruffling membranes in a Rac-dependent way. The novelty of these findings is in respect to the demonstration that the correct positioning at the ruffling membranes is crucial for the subsequent series of events that leads to IkBalpha proteasomal degradation and the resultant activation of NF-kappaB. Consequently, this points to the role of Rac as a docking molecule in NF-kappaB activation.

MeSH Terms
Adaptor Proteins, Signal Transducing Cell Cycle Proteins/metabolism Cell Membrane/metabolism Cell Nucleus/metabolism Cells, Cultured Cullin Proteins/metabolism Cysteine Endopeptidases/metabolism Humans I-kappa B Proteins/metabolism Multienzyme Complexes/metabolism NF-kappa B/metabolism Proteasome Endopeptidase Complex S-Phase Kinase-Associated Proteins/metabolism SKP Cullin F-Box Protein Ligases/metabolism Transcription Factors/metabolism beta-Transducin Repeat-Containing Proteins/metabolism rac GTP-Binding Proteins/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Cell Cycle Proteins Cullin 1 Cullin Proteins I-kappa B Proteins Multienzyme Complexes NF-kappa B NUB1 protein, human S-Phase Kinase-Associated Proteins Transcription Factors beta-Transducin Repeat-Containing Proteins SKP Cullin F-Box Protein Ligases Cysteine Endopeptidases Proteasome Endopeptidase Complex rac GTP-Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Boyer Laurent
Institut National de la Santé et de la Recherche Médicale U452, IFR50, Faculté de Médecine, 06107 Nice, France.
Travaglione Sara
Falzano Loredana
Gauthier Nils C
Popoff Michel R
Lemichez Emmanuel
Fiorentini Carla
Fabbri Alessia
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-05-0301
Published
2004-03-00
Epub
2003-00-10
Pages
1124-33
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC363090
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-05-0301 PMC Full Text View journal details
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