TAK1-TABs Complex: A Central Signalosome in Inflammatory Responses

Xu, Yanran; Lei, Cao-Qi

doi:10.3389/fimmu.2020.608976

Cited by 126 publications

(104 citation statements)

References 136 publications

(206 reference statements)

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“…The NF-κB transcription factor is localized in the cytosol associated with inhibitor proteins IκBs as an inactivated trimer. The phosphorylation of the inhibitory subunit IκB by IκB Kinases (IKKs) triggers its dissociation and translocation of the remaining active dimeric NF-κB to the nucleus, activating pro-inflammatory target genes [ 70 , 71 ].…”

Section: The Anti-inflammatory Compounds Present In the Diet: Classification And Mechanism Of Actionmentioning

confidence: 99%

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Anti-Inflammatory Properties of Diet: Role in Healthy Aging

et al. 2021

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Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.

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Section: The Anti-inflammatory Compounds Present In the Diet: Classification And Mechanism Of Actionmentioning

confidence: 99%

“…TAK1 activation requires assembling with TAK-1 binding proteins (TAB1, TAB2 and TAB3). The resulting TAK1-TABs complex phosphorylates the IκB Kinase β (IKKβ), thus leading to NF-κB activation [ 70 , 71 ].…”

Section: The Anti-inflammatory Compounds Present In the Diet: Classification And Mechanism Of Actionmentioning

confidence: 99%

Anti-Inflammatory Properties of Diet: Role in Healthy Aging

et al. 2021

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“…Tumor necrosis factor (TNF) α and IL-6 were also able to induce ADAMTS4 and ADAMTS5 mRNA expression in synovial cells consistent with a regulation of these two ADAMTS proteases by pro-inflammatory cytokines ( Mimata et al, 2012 ; Uchida et al, 2017 ). Signal transduction of TNFα in synovial cells involved TAK1, a MAP kinase (MAPK) that can transduce signals originating from several cytokines ( Xu and Lei, 2020 ). IL-6 signaling was mediated by MAPK, ERK1/2 and MEK.…”

Section: Transcriptional and Posttranscriptional Regulation Of Adamts Proteasesmentioning

confidence: 99%

Regulation of ADAMTS Proteases

Rose

Taye

Karoulias

et al. 2021

Front. Mol. Biosci.

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A disintegrin and metalloprotease with thrombospondin type I motifs (ADAMTS) proteases are secreted metalloproteinases that play key roles in the formation, homeostasis and remodeling of the extracellular matrix (ECM). The substrate spectrum of ADAMTS proteases can range from individual ECM proteins to entire families of ECM proteins, such as the hyalectans. ADAMTS-mediated substrate cleavage is required for the formation, remodeling and physiological adaptation of the ECM to the needs of individual tissues and organ systems. However, ADAMTS proteases can also be involved in the destruction of tissues, resulting in pathologies such as arthritis. Specifically, ADAMTS4 and ADAMTS5 contribute to irreparable cartilage erosion by degrading aggrecan, which is a major constituent of cartilage. Arthritic joint damage is a major contributor to musculoskeletal morbidity and the most frequent clinical indication for total joint arthroplasty. Due to the high sequence homology of ADAMTS proteases in their catalytically active site, it remains a formidable challenge to design ADAMTS isotype-specific inhibitors that selectively inhibit ADAMTS proteases responsible for tissue destruction without affecting the beneficial functions of other ADAMTS proteases. In vivo, proteolytic activity of ADAMTS proteases is regulated on the transcriptional and posttranslational level. Here, we review the current knowledge of mechanisms that regulate ADAMTS protease activity in tissues including factors that induce ADAMTS gene expression, consequences of posttranslational modifications such as furin processing, the role of endogenous inhibitors and pharmacological approaches to limit ADAMTS protease activity in tissues, which almost exclusively focus on inhibiting the aggrecanase activity of ADAMTS4 and ADAMTS5.

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“…Diverse ligands including TLRs, IL-1 and TNF activate TAK1 through assembly with the TAK-1 binding proteins (TAB1-3), initiating cellular signaling and activation of NF- κ B and MAPKs [ 278 ] ( Figure 5 ). TAK1 itself plays a role in the cellular responses to environmental stress during inflammation and is a key mediator in the regulation of cell survival and death in cancers and inflammatory diseases [ 279 ].…”

Section: Inhibiting Nf-κb In Pdac; Is Therapy Possible Without Unwanted Side-effects?mentioning

confidence: 99%

NF-κB and Pancreatic Cancer; Chapter and Verse

O’Reilly

2021

Cancers

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Pancreatic Ductal Adenocarcinoma (PDAC) is one of the world’s most lethal cancers. An increase in occurrence, coupled with, presently limited treatment options, necessitates the pursuit of new therapeutic approaches. Many human cancers, including PDAC are initiated by unresolved inflammation. The transcription factor NF-κB coordinates many signals that drive cellular activation and proliferation during immunity but also those involved in inflammation and autophagy which may instigate tumorigenesis. It is not surprising therefore, that activation of canonical and non-canonical NF-κB pathways is increasingly recognized as an important driver of pancreatic injury, progression to tumorigenesis and drug resistance. Paradoxically, NF-κB dysregulation has also been shown to inhibit pancreatic inflammation and pancreatic cancer, depending on the context. A pro-oncogenic or pro-suppressive role for individual components of the NF-κB pathway appears to be cell type, microenvironment and even stage dependent. This review provides an outline of NF-κB signaling, focusing on the role of the various NF-κB family members in the evolving inflammatory PDAC microenvironment. Finally, we discuss pharmacological control of NF-κB to curb inflammation, focussing on novel anti-cancer agents which reinstate the process of cancer cell death, the Smac mimetics and their pre-clinical and early clinical trials.

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TAK1-TABs Complex: A Central Signalosome in Inflammatory Responses

Cited by 126 publications

References 136 publications

Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Regulation of ADAMTS Proteases

NF-κB and Pancreatic Cancer; Chapter and Verse

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