The alternative NF-κB pathway from biochemistry to biology: Pitfalls and promises for future drug development

Dejardin, Emmanuel

doi:10.1016/j.bcp.2006.08.007

Cited by 328 publications

(323 citation statements)

References 141 publications

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“…The p52/RelB dimers have higher affinity for distinct B elements (29). This pathway plays a crucial role in controlling the development and function of secondary lymphoid organs (29,32).…”

Section: Introductionmentioning

confidence: 99%

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

et al. 2009

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There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B (NF-B), a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-B activation in inflammatory bowel diseases (

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Section: Introductionmentioning

confidence: 99%

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

et al. 2009

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“…[29][30][31][32][33][34] c-IAP1/2 depletion leads to NIK (NF-κB-inducing kinase) stabilization and the phosphorylation of both IKKα and NF-κB2/p100 prior to the processing of p100 into p52, a pathway defined as the alternative, or non-canonical, NF-κB pathway. [35][36][37] Genetic mouse models revealed that NIK is required for the proper development and/or maintenance of secondary lymphoid organs, for osteoclastogenesis, for T-cell activation as well for B-cell survival. 35,38,39 In this paper, we highlight an unexpected role for NIK in TNFR1-induced cell death.…”

mentioning

confidence: 99%

“…[35][36][37] Genetic mouse models revealed that NIK is required for the proper development and/or maintenance of secondary lymphoid organs, for osteoclastogenesis, for T-cell activation as well for B-cell survival. 35,38,39 In this paper, we highlight an unexpected role for NIK in TNFR1-induced cell death. We found that NIK diverges from the alternative NF-κB pathway to promote cell death.…”

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confidence: 99%

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

et al. 2015

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NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTβR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex.In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTβR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.

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“…Dans cette revue, nous tenterons de faire l'état des lieux des données actuelles portant sur l'implication de la voie alternative et, plus particulièrement, de RelB et de IKKα, dans le processus tumoral. < induite par différents membres de la superfamille du TNF (tumor necrosis factor) (CD40L, lymphotoxine β, BAFF ou B cell-activating factor belonging to the TNF family…), des protéines virales (LMP1 du virus EBV ou Epstein-Barr virus, Tax du virus HTLV1 ou human T lymphotropic virus 1…) ou la souche bactérienne Gram-Helicobacter pylori, et repose sur la protéolyse induite de la protéine p100, l'inhibiteur principal de RelB [9]. En l'absence d'activation, les dimères RelB/p50 et RelB/p52 sont séquestrés dans le cytoplasme via leur association avec p100.…”

Section: Voie Canonique Et Voie Alternative D'activation De Nf-kbunclassified

“…Il est intéressant de noter que le rôle leucémo-gène de RelB s'exerce dans les cellules stromales radio-résistantes et non dans le compartiment hématopoïétique. Des remaniements du gène codant p100, l'inhibiteur principal de RelB, ont également été associés au développement de nombreuses pathologies hématopoïétiques malignes [9]. Ils sont fréquemment observés dans les lymphomes T cutanés, et plus rarement dans les lymphomes B non hodgkiniens, les leucémies lymphocytaires B chroniques et les myélomes multiples.…”

Section: Voie Alternative De Nf-kb Et Développement De Cancers Activaunclassified

Voie alternative d’activation de NF-κB et cancer

Baud

Jacque

2008

Med Sci (Paris)

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Une vingtaine d'années après leur découverte, l'intérêt que suscitent les facteurs de transcription NF-κB (nuclear factor kB) émane de la multiplicité des réponses cellulaires auxquelles ces facteurs sont associés. Ils jouent en effet un rôle central dans la réponse inflammatoire, l'immunité innée et acquise, la balance survie/mort cellulaire, mais aussi la tumorigenèse [1][2][3][4][5]. Ainsi, une dérégulation de l'activité des facteurs NF-κB, via la production de formes anormales de NF-κB, ou un défaut de leurs activités transcriptionnelles, est retrouvée de manière récurrente dans des lymphomes et des leucémies, mais aussi dans des tumeurs solides [5, 37]. Plus récemment, il a été mis en évidence que les facteurs NF-κB participent également au dévelop-pement des tumeurs en activant des gènes de résistance à l'apoptose, rendant certaines tumeurs résistantes aux traitements chimiothéra-peutiques et radiothérapeutiques [6].

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The alternative NF-κB pathway from biochemistry to biology: Pitfalls and promises for future drug development

Cited by 328 publications

References 141 publications

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

Voie alternative d’activation de NF-κB et cancer

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