PMID- 23086447
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20220408
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 13
IP  - 12
DP  - 2012 Dec
TI  - Control of RelB during dendritic cell activation integrates canonical and 
      noncanonical NF-kappaB pathways.
PG  - 1162-70
LID - 10.1038/ni.2446 [doi]
AB  - The NF-kappaB protein RelB controls dendritic cell (DC) maturation and may be 
      targeted therapeutically to manipulate T cell responses in disease. Here we 
      report that RelB promoted DC activation not as the expected RelB-p52 effector of 
      the noncanonical NF-kappaB pathway, but as a RelB-p50 dimer regulated by canonical 
      IkappaBs, IkappaBalpha and IkappaBvarepsilon. IkappaB control of RelB minimized spontaneous maturation but 
      enabled rapid pathogen-responsive maturation. Computational modeling of the NF-kappaB 
      signaling module identified control points of this unexpected cell type-specific 
      regulation. Fibroblasts that we engineered accordingly showed DC-like RelB 
      control. Canonical pathway control of RelB regulated pathogen-responsive gene 
      expression programs. This work illustrates the potential utility of systems 
      analyses in guiding the development of combination therapeutics for modulating 
      DC-dependent T cell responses.
FAU - Shih, Vincent F-S
AU  - Shih VF
AD  - Signaling Systems Laboratory, Department of Chemistry and Biochemistry and San 
      Diego Center for Systems Biology, University of California, San Diego, La Jolla, 
      California, USA.
FAU - Davis-Turak, Jeremy
AU  - Davis-Turak J
FAU - Macal, Monica
AU  - Macal M
FAU - Huang, Jenny Q
AU  - Huang JQ
FAU - Ponomarenko, Julia
AU  - Ponomarenko J
FAU - Kearns, Jeffrey D
AU  - Kearns JD
FAU - Yu, Tony
AU  - Yu T
FAU - Fagerlund, Riku
AU  - Fagerlund R
FAU - Asagiri, Masataka
AU  - Asagiri M
FAU - Zuniga, Elina I
AU  - Zuniga EI
FAU - Hoffmann, Alexander
AU  - Hoffmann A
LA  - eng
SI  - GEO/GSE34990
GR  - GM071573/GM/NIGMS NIH HHS/United States
GR  - GM085325/GM/NIGMS NIH HHS/United States
GR  - P01 GM071862/GM/NIGMS NIH HHS/United States
GR  - AI090935/AI/NIAID NIH HHS/United States
GR  - AI081923/AI/NIAID NIH HHS/United States
GR  - R01 AI083453/AI/NIAID NIH HHS/United States
GR  - R01 AI081923/AI/NIAID NIH HHS/United States
GR  - P50 GM085764/GM/NIGMS NIH HHS/United States
GR  - R01 GM071573/GM/NIGMS NIH HHS/United States
GR  - R01 GM085325/GM/NIGMS NIH HHS/United States
GR  - GM085763/GM/NIGMS NIH HHS/United States
GR  - P01 AI090935/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121021
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (NF-kappa B)
RN  - 0 (Relb protein, mouse)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 9)
RN  - 147337-75-5 (Transcription Factor RelB)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
CIN - Nat Immunol. 2012 Dec;13(12):1139-41. PMID: 23160209
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cell Line
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Fibroblasts/metabolism
MH  - Gene Expression Regulation
MH  - I-kappa B Kinase/metabolism
MH  - *Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/genetics/*metabolism
MH  - Protein Multimerization
MH  - Signal Transduction
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Toll-Like Receptor 9/metabolism
MH  - Transcription Factor RelB/genetics/*metabolism
PMC - PMC3634611
MID - NIHMS404259
EDAT- 2012/10/23 06:00
MHDA- 2013/01/18 06:00
PMCR- 2013/06/01
CRDT- 2012/10/23 06:00
PHST- 2011/11/28 00:00 [received]
PHST- 2012/08/29 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - ni.2446 [pii]
AID - 10.1038/ni.2446 [doi]
PST - ppublish
SO  - Nat Immunol. 2012 Dec;13(12):1162-70. doi: 10.1038/ni.2446. Epub 2012 Oct 21.