Oscillations in NF-kappaB signaling control the dynamics of gene expression.
Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus. NF-kappaB regulation of IkappaBalpha transcription represents a delayed negative feedback loop that drives oscillations in NF-kappaB translocation. Single-cell time-lapse imaging and computational modeling of NF-kappaB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IkappaBalpha transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations.
Nelson
D E
DE
Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK.
Ihekwaba
A E C
AE
Elliott
M
M
Johnson
J R
JR
Gibney
C A
CA
Foreman
B E
BE
Nelson
G
G
See
V
V
Horton
C A
CA
Spiller
D G
DG
Edwards
S W
SW
McDowell
H P
HP
Unitt
J F
JF
Sullivan
E
E
Grimley
R
R
Benson
N
N
Broomhead
D
D
Kell
D B
DB
White
M R H
MR
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D005047:Etoposide