Regulation of NF-κB-Dependent Lymphocyte Activation and Development by Paracaspase

Ruefli-Brasse, Astrid; French, Dorothy; Dixit, Vishva M.

doi:10.1126/science.1090769

Cited by 351 publications

(408 citation statements)

References 16 publications

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“…Consistent with these results, transgenic mice expressing Eµ-API2-MALT1 have elevated NF-κB activity [46]. On the other hand, genetic inactivation of Malt1 gene in mice impairs TCR-induced NF-κB activation [47,48]. However, there are some discrepancies about the role of MALT1 in BCR-induced NF-κB activation in two mouse models.…”

Section: Cbm Proteins In Antigen Receptor Signalingsupporting

confidence: 65%

“…However, there are some discrepancies about the role of MALT1 in BCR-induced NF-κB activation in two mouse models. One study suggests that total NF-κB activity is significantly reduced in MALT1-deficient B cells [47], whereas another gene-targeting study shows that NF-κB activation is almost not affected by MALT1 deficiency upon BCR stimulation [48]. Surprisingly, further work has revealed that the activation of c-Rel isoform of NF-κB is more severely impaired than other isoforms, such as RelA (known as p65) [49].…”

Section: Cbm Proteins In Antigen Receptor Signalingmentioning

confidence: 99%

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NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

172

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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Section: Cbm Proteins In Antigen Receptor Signalingsupporting

confidence: 65%

Section: Cbm Proteins In Antigen Receptor Signalingmentioning

confidence: 99%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

172

201

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“…This notion is supported by data from the mice deficient in PKC-b, CARMA1, MALT and Bcl10, which indicate that these molecules are largely dispensable for overall B cell development and survival [17,[54][55][56]. However, all these knockout mice showed specific B cell defects such as complete absence of B1 B cell compartment and defected terminal differentiation of immature B cells into MZ B cells in the spleen [17,[54][55][56]. Strikingly, splenic B cells from all these mice are also defective in CD40-induced proliferation.…”

Section: Discussionmentioning

confidence: 81%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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NF‐κB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen‐mediated activation of B cells. CARD domain and MAGUK‐domain containing protein‐1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR‐induced NF‐κB activation. CARMA1‐deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1‐deficient B cells are also defective in CD40‐induced proliferation. The mechanisms responsible for CD40‐induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1‐deficient B cells. Instead, we have found that the defective proliferation of CARMA1‐deficient B cells is due to two events. First, CARMA1‐deficient B cells show defective cell‐cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1‐deficient mice. Since B cell maturation requires basal signaling through BCR and NF‐κB activation, we propose that impaired BCR signaling in CARMA1‐deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.

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“…Another potential non-canonical NF-κB signaling component is MALT1, a para-caspase initially identified as a component of antigen receptor-stimulated canonical NF-κB pathway [83,84]. Unlike its essential role in TCR signaling, MALT1 is largely dispensable for canonical NF-κB activation by BCR [84].…”

Section: Nik Regulatorsmentioning

confidence: 99%

Non-canonical NF-κB signaling pathway

2010

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The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-κB-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, IκB kinase-α (IKKα), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-κB signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.

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Regulation of NF-κB-Dependent Lymphocyte Activation and Development by Paracaspase

Cited by 351 publications

References 16 publications

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Non-canonical NF-κB signaling pathway

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