Online citations, reference lists, and bibliographies.
← Back to Search

Induction Of Gadd45β By NF-κB Downregulates Pro-apoptotic JNK Signalling

E. Smaele, F. Zazzeroni, S. Papa, D. U. Nguyen, R. Jin, Joy Jones, R. Cong, G. Franzoso
Published 2001 · Biology

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
In addition to coordinating immune and inflammatory responses, NF-κB/Rel transcription factors control cell survival. Normally, NF-κB dimers are sequestered in the cytoplasm by binding to inhibitory IκB proteins, and can be activated rapidly by signals that induce the sequential phosphorylation and proteolysis of IκBs. Activation of NF-κB antagonizes apoptosis or programmed cell death by numerous triggers, including the ligand engagement of ‘death receptors’ such as tumour-necrosis factor (TNF) receptor. The anti-apoptotic activity of NF-κB is also crucial to oncogenesis and to chemo- and radio-resistance in cancer. Cytoprotection by NF-κB involves the activation of pro-survival genes; however, its basis remains poorly understood. Here we report that NF-κB complexes downregulate the c-Jun amino-terminal kinase (JNK) cascade, thus establishing a link between the NF-κB and the JNK pathways. This link involves the transcriptional upregulation of gadd45β/myd118 (ref. 4), which downregulates JNK signalling induced by the TNF receptor (TNF-R). This NF-κB-dependent inhibition of the JNK pathway is central to the control of cell death. Our findings define a protective mechanism that is mediated by NF-κB complexes and establish a role for the persistent activation of JNK in the apoptotic response to TNF-α.
This paper references
10.1126/science.274.5288.782
An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
A. Beg (1996)
10.1126/science.271.5248.521
Interfering with Apoptosis: Ca2+-Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3
Pasquale Vito (1996)
The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21WAF1/CIP1.
M. Vairapandi (1996)
10.1126/science.274.5288.787
Suppression of TNF-α-Induced Apoptosis by NF-κB
D. V. Van Antwerp (1996)
10.1073/PNAS.94.19.10057
Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control.
Z. Chu (1997)
10.1074/jbc.272.40.24751
Identification of c-Jun NH2-terminal Protein Kinase (JNK)-activating Kinase 2 as an Activator of JNK but Not p38*
X. Lu (1997)
10.1016/S1074-7613(00)80449-5
Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b.
S. Huang (1997)
10.1074/JBC.273.7.4027
Correlation between Sustained c-Jun N-terminal Protein Kinase Activation and Apoptosis Induced by Tumor Necrosis Factor-α in Rat Mesangial Cells*
Yan-Lin Guo (1998)
10.1146/ANNUREV.IMMUNOL.16.1.225
NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
S. Ghosh (1998)
10.1016/S0092-8674(00)81619-0
A Family of Stress-Inducible GADD45-like Proteins Mediate Activation of the Stress-Responsive MTK1/MEKK4 MAPKKK
M. Takekawa (1998)
10.1016/S1074-7613(00)80456-2
Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes.
E. Jacinto (1998)
10.1126/SCIENCE.281.5383.1680
NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.
C. Wang (1998)
10.1074/jbc.274.27.19368
The Human Tumor Necrosis Factor (TNF) Receptor-associated Factor 1 Gene (TRAF1) Is Up-regulated by Cytokines of the TNF Ligand Family and Modulates TNF-induced Activation of NF-κB and c-Jun N-terminal Kinase*
Ralph Schwenzer (1999)
10.1074/jbc.274.42.29599
gadd45 Is Not Required for Activation of c-Jun N-terminal Kinase or p38 during Acute Stress*
X. Wang (1999)
10.1101/GAD.13.4.382
The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFα-induced apoptosis
Wei-Xing Zong (1999)
10.1038/sj.onc.1202885
CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control
Wei Zhang (1999)
10.1146/ANNUREV.CELLBIO.15.1.269
Biochemical pathways of caspase activation during apoptosis.
I. Budihardjo (1999)
10.1074/jbc.274.42.29595
Stress-induced JNK Activation Is Independent of Gadd45 Induction*
E. Shaulian (1999)
10.1038/sj.onc.1202667
Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45
Q. Zhan (1999)
10.1074/JBC.M908925199
A1 Functions at the Mitochondria to Delay Endothelial Apoptosis in Response to Tumor Necrosis Factor*
P. Duriez (2000)
10.1128/MCB.20.15.5665-5679.2000
Identification of the Cytolinker Plectin as a Major Early In Vivo Substrate for Caspase 8 during CD95- and Tumor Necrosis Factor Receptor-Mediated Apoptosis
A. Stegh (2000)
10.3892/IJO.16.4.651
The c-Jun N-terminal kinase pathway and apoptotic signaling (review).
Y. Chen (2000)
10.1128/MCB.20.8.2687-2695.2000
The Rel/NF-κB Family Directly Activates Expression of the Apoptosis Inhibitor Bcl-xL
Cailin Chen (2000)
10.4049/jimmunol.165.9.5084
TNFR-Associated Factor Family Protein Expression in Normal Tissues and Lymphoid Malignancies
J. Zapata (2000)
10.1016/S0092-8674(00)00116-1
Signal Transduction by the JNK Group of MAP Kinases
R. Davis (2000)
10.1016/S1074-7613(01)00141-8
GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells.
B. Lu (2001)
10.1172/JCI11991
Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB.
A. Baldwin (2001)
10.1038/sj.onc.1204061
Expression of the NF-κB target gene IEX-1 (p22/PRG1) does not prevent cell death but instead triggers apoptosis in Hela cells
A. Arlt (2001)
10.1093/embo-reports/kve046
ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
K. Tobiume (2001)
10.1038/35065000
Mammalian MAP kinase signalling cascades
Lufen Chang (2001)



This paper is referenced by
10.3389/fphys.2021.679166
Ras-Related C3 Botulinum Toxin Substrate 1 Combining With the Mixed Lineage Kinase 3- Mitogen-Activated Protein Kinase 7- c-Jun N-Terminal Kinase Signaling Module Accelerates Diabetic Nephropathy
C. Ying (2021)
OTT_A_281450 255..269
Lanqing Gong (2021)
10.1126/scitranslmed.aba6480
iPSC–endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension
Mingxia Gu (2021)
10.2147/OTT.S281450
GADD45B Facilitates Metastasis of Ovarian Cancer Through Epithelial–Mesenchymal Transition
Lanqing Gong (2021)
10.1186/s13027-021-00390-3
Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma
Shahrzad Shadabi (2021)
10.1007/978-3-030-49844-3_1
Protein Kinase-Mediated Decision Between the Life and Death.
A. Engin (2021)
10.1007/s11064-021-03360-8
Spata2 Knockdown Exacerbates Brain Inflammation via NF-κB/P38MAPK Signaling and NLRP3 Inflammasome Activation in Cerebral Ischemia/Reperfusion Rats.
Yikun Ren (2021)
10.1038/s41540-021-00204-7
IκBα is required for full transcriptional induction of some NFκB-regulated genes in response to TNF in MCF-7 cells
(2021)
10.1186/s13578-021-00530-7
Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway
Xiuhao Zhao (2021)
10.1007/978-1-0716-1669-7_21
The Screening of Combinatorial Peptide Libraries for Targeting Key Molecules or Protein-Protein Interactions in the NF-κB Pathway.
Laura Tornatore (2021)
10.1038/s41419-020-03298-9
Deletion of IKK2 in haematopoietic cells of adult mice leads to elevated interleukin-6, neutrophilia and fatal gastrointestinal inflammation
Karla C Fischer (2021)
10.1111/jcmm.15519
Ablation of Gadd45β ameliorates the inflammation and renal fibrosis caused by unilateral ureteral obstruction
Sung-Je Moon (2020)
10.1038/s41419-020-2399-y
Life, death, and autophagy in cancer: NF-κB turns up everywhere
Daniela Verzella (2020)
10.1074/jbc.RA120.012943
Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells
Keesiang Lim (2020)
10.1007/s00011-020-01426-x
Burn injury induces elevated inflammatory traffic: the role of NF-κB
Benu George (2020)
10.1098/rsos.192152
Mathematical modelling of the role of GADD45β in the pathogenesis of multiple myeloma
Yao Zhang (2020)
10.3390/s20010015
Designing Silver Nanoparticles for Detecting Levodopa (3,4-Dihydroxyphenylalanine, L-Dopa) Using Surface-Enhanced Raman Scattering (SERS)
R. Rubira (2019)
10.3389/fcell.2020.584653
Distinct Factors Secreted by Adipose Stromal Cells Protect the Endothelium From Barrier Dysfunction and Apoptosis
Hongyan Lu (2020)
10.33448/RSD-V9I10.9231
Curcumin promotes extrinsic apoptosis in canine osteosarcoma cells
Nayane Peixoto Soares (2020)
10.1016/j.ejphar.2020.173419
Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells
S. Messeha (2020)
10.3389/fimmu.2020.579266
Non-Transcriptional and Translational Function of Canonical NF-κB Signaling in Activating ERK1/2 in IL-1β-Induced COX-2 Expression in Synovial Fibroblasts
R. Nakano (2020)
10.1111/1756-185X.13958
Nuclear factor‐κB in rheumatoid arthritis
J. Li (2020)
10.1007/978-3-319-99375-1_36
Molecular Mechanisms of Apoptosis in Naive and Memory Human T Cell Subsets
Sudhir Gupta (2019)
10.1038/s12276-019-0335-y
Gadd45β promotes regeneration after injury through TGFβ-dependent restitution in experimental colitis
J. Hwang (2019)
10.1016/J.JTCVS.2019.02.091
Transcriptome profiling reveals activation of inflammation and apoptosis in the neonatal striatum after deep hypothermic circulatory arrest.
Lan N. Tu (2019)
10.3390/genes10050378
Role of D-GADD45 in JNK-Dependent Apoptosis and Regeneration in Drosophila
Carlos Camilleri-Robles (2019)
10.1080/00498254.2018.1490044
Liver-specific knockout of histone methyltransferase G9a impairs liver maturation and dysregulates inflammatory, cytoprotective, and drug-processing genes
Hong Lu (2018)
10.1111/bjh.15569
Clinical proof of concept for a safe and effective NF‐κB‐targeting strategy in multiple myeloma
Laura Tornatore (2018)
10.1007/s12031-019-01284-1
Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats
Ali Mohamed Choucry (2019)
10.1038/s41467-018-07927-y
BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity
A. Heijink (2019)
10.1016/j.toxrep.2019.04.006
Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3
Laura Tornatore (2019)
Decitabine reverses gefitinib resistance in PC9 lung adenocarcinoma cells by demethylation of RASSF1A and GADD45β promoter.
Tao Hou (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar