Activation of NF-κB in B cell receptor signaling through Bruton’s tyrosine kinase-dependent phosphorylation of IκB-α

Pontoriero, Marilena; Fiume, Giuseppe; Vecchio, Eleonora; Laurentiis, Annamaria de; Albano, Fabio; Iaccino, Enrico; Mimmi, Selena; Pisano, Antonio; Agosti, Valter; Giovannone, Emilia Dora; Altobelli, Annalisa; Caiazza, Carmen; Mallardo, Massimo; Scala, Giuseppe; Quinto, Ileana

doi:10.1007/s00109-019-01777-x

Cited by 43 publications

(37 citation statements)

References 49 publications

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“…This promoted the dissociation of the IκBα-NF-κB complex and the phosphorylation and nuclear translocation of p65 but did not affect IκBα degradation (Takada et al, 2003). Similarly, in anti-IgM-stimulated B cell, Btk is rapidly activated; thereafter, it then phosphorylates IκBα at Tyr305 and Tyr289 residues in the cytosol and associates with phosphorylated IκBα, which correlates with the nuclear translocation of p65 and mediated the early transcriptional activation of NF-κB-responsive genes activated via B cell receptor triggering (Pontoriero et al, 2019). Btk and NF-κB are upregulated in acute and chronic lymphocytic leukemia (Pal Singh et al, 2018).…”

Section: Tyrosine Kinase-dependent Phosphorylationmentioning

confidence: 90%

Post-translational Modifications of IκBα: The State of the Art

Wang

Peng

Huang

et al. 2020

Front. Cell Dev. Biol.

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The nuclear factor-kappa B (NF-κB) signaling pathway regulates a variety of biological functions in the body, and its abnormal activation contributes to the pathogenesis of many diseases, such as cardiovascular and respiratory diseases and cancers. Therefore, to ensure physiological homeostasis of body systems, this pathway is strictly regulated by IκBα transcription, IκBα synthesis, and the IκBα-dependent nuclear transport of NF-κB. Particularly, the post-translational modifications of IκBα including phosphorylation, ubiquitination, SUMOylation, glutathionylation and hydroxylation are crucial in the abovementioned regulatory process. Because of the importance of the NF-κB pathway in maintaining body homeostasis, understanding the post-translational modifications of IκBα can not only provide deeper insights into the regulation of NF-κB pathway but also contribute to the development of new drug targets and biomarkers for the diseases.

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Section: Tyrosine Kinase-dependent Phosphorylationmentioning

confidence: 90%

Post-translational Modifications of IκBα: The State of the Art

Wang

Peng

Huang

et al. 2020

Front. Cell Dev. Biol.

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“…Compromised apoptotic signaling promote tumorigenesis, particularly together with oncogenic lesions that drive excess cell proliferation [ 105 , 106 ]. MYC gene alterations have been identified in B-cell neoplasms, and are usually associated with aggressive clinical behavior.…”

Section: Conclusion and Remarksmentioning

confidence: 99%

Insights about MYC and Apoptosis in B-Lymphomagenesis: An Update from Murine Models

Vecchio

Fiume

Correnti

et al. 2020

IJMS

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The balance between cell survival and cell death represents an essential part of human tissue homeostasis, while altered apoptosis contributes to several pathologies and can affect the treatment efficacy. Impaired apoptosis is one of the main cancer hallmarks and some types of lymphomas harbor mutations that directly affect key regulators of cell death (such as BCL-2 family members). The development of novel techniques in the field of immunology and new animal models has greatly accelerated our understanding of oncogenic mechanisms in MYC-associated lymphomas. Mouse models are a powerful tool to reveal multiple genes implicated in the genesis of lymphoma and are extensively used to clarify the molecular mechanism of lymphoma, validating the gene function. Key features of MYC-induced apoptosis will be discussed here along with more recent studies on MYC direct and indirect interactors, including their cooperative action in lymphomagenesis. We review our current knowledge about the role of MYC-induced apoptosis in B-cell malignancies, discussing the transcriptional regulation network of MYC and regulatory feedback action of miRs during MYC-driven lymphomagenesis. More importantly, the finding of new modulators of apoptosis now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.

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“…Several data demonstrate that specific genes are deregulated in intracellular pathways involved in B cell tumorigenesis and can be targeted with tumor-and patient-specific therapy [110,117,118]. By analyzing the deregulated CLL exosomal proteins or miRNAs in the blood of patients we could have reliable tool for rapid diagnosis of disease recurrence and selection of the most appropriate tumor-targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Role of Chronic Lymphocytic Leukemia (CLL)-Derived Exosomes in Tumor Progression and Survival

et al. 2020

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Chronic lymphocytic leukemia (CLL) is a B-lymphoproliferative disease, which consists of the abnormal proliferation of CD19/CD5/CD20/CD23 positive lymphocytes in blood and lymphoid organs, such as bone marrow, lymph nodes and spleen. The neoplastic transformation and expansion of tumor B cells are commonly recognized as antigen-driven processes, mediated by the interaction of antigens with the B cell receptor (BCR) expressed on the surface of B-lymphocytes. The survival and progression of CLL cells largely depend on the direct interaction of CLL cells with receptors of accessory cells of tumor microenvironment. Recently, much interest has been focused on the role of tumor release of small extracellular vesicles (EVs), named exosomes, which incorporate a wide range of biologically active molecules, particularly microRNAs and proteins, which sustain the tumor growth. Here, we will review the role of CLL-derived exosomes as diagnostic and prognostic biomarkers of the disease.

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Activation of NF-κB in B cell receptor signaling through Bruton’s tyrosine kinase-dependent phosphorylation of IκB-α

Cited by 43 publications

References 49 publications

Post-translational Modifications of IκBα: The State of the Art

Post-translational Modifications of IκBα: The State of the Art

Insights about MYC and Apoptosis in B-Lymphomagenesis: An Update from Murine Models

Role of Chronic Lymphocytic Leukemia (CLL)-Derived Exosomes in Tumor Progression and Survival

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