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I?B?: an emerging player in cancer.

ABSTRACT: I?B?, an atypical member of the nuclear I?B family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NF?B-dependent pathway. Like its homolog Bcl3, I?B? can regulate the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-?B. Long studied as a key component of the immune response, I?B? emerges as an important regulator of inflammation, cell proliferation and survival. As a result, growing evidence support the role of this transcription factor in the pathogenesis number of human hematological and solid malignancies.

SUBMITTER: Willems M

PROVIDER: S-EPMC5323236 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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IκBζ: an emerging player in cancer.

Willems Marie M Dubois Nadège N Musumeci Lucia L Bours Vincent V Robe Pierre A PA

Oncotarget 20161001 40

IκBζ, an atypical member of the nuclear IκB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NFκB-dependent pathway. Like its homolog Bcl3, IκBζ can regulate the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. Long studied as a key component of the immune response, IκBζ emerges as an important regulator of inflammation, cell proliferat ...[more]

PMID: 27579619

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TGF-?: an emerging player in drug resistance.

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| S-EPMC3875670 | biostudies-literature

UFMylation System: An Emerging Player in Tumorigenesis.

Project description:Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule (UBLs), is evolutionarily expressed in multiple species except yeast. Similarly to ubiquitin, UFM1 is covalently attached to its substrates through a well-orchestrated three-step enzymatic reaction involving E1, the UFM1-activating enzyme (ubiquitin-like modifier-activating enzyme 5, UBA5); E2, the UFM1-conjugating enzyme 1 (UFC1); and E3, the UFM1-specific ligase 1 (UFL1). To date, numerous studies have shown that UFM1 modification is implicated in various cellular processes, including endoplasmic reticulum (ER) stress, DNA damage response and erythroid development. An abnormal UFM1 cascade is closely related to a variety of diseases, especially tumors. Herein, we summarize the process and functions of UFM1 modification, illustrating the relationship and mechanisms between aberrant UFMylation and diversified tumors, aiming to provide novel diagnostic biomarkers or therapeutic targets for cancer treatments.

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CircRNA cPWWP2A: an emerging player in diabetes mellitus.

Project description:Circular RNAs(CircRNAs), a new class of non-coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455-7464, 2019) shown that a novel diabetic retinopathy (DR)-associated CircRNA cPWWP2A, which could act as a competing endogenous RNA interacting with miR-579 to promote the DR-induced retinal vascular dysfunction through up-regulating the expression of Angiopoietin 1, Occludin, and SIRT1. Their findings may provide new insight into the potential use of CircRNA cPWWP2A for the targeted therapy of DR. However, those promising findings may need to be further evaluated detailedly for the following reason. (1) This study doesn't well clarify why the most significantly up-regulated CircRNA mmu _circ_0000254 the fold change of which is 160.581 is excluded,while the cPWWP2A the fold change of which is only 3.487 is chosen. (2) It is difficult to conclude that cPWWP2A competing with miR-579 only by the analysis of colocalization in pericytes.

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miR-191: an emerging player in disease biology.

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Bruton's Tyrosine Kinase: An Emerging Key Player in Innate Immunity.

Project description:Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.

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The fibroblast: An emerging key player in thymic T cell selection.

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Project description:The Wnt pathway, which comprises the canonical and non-canonical pathways, is an evolutionarily conserved mechanism that regulates crucial biological aspects throughout the development and adulthood. Emergence and patterning of the nervous and vascular systems are intimately coordinated, a process in which Wnt pathway plays particularly important roles. In the brain, Wnt ligands activate a cell-specific surface receptor complex to induce intracellular signaling cascades regulating neurogenesis, synaptogenesis, neuronal plasticity, synaptic plasticity, angiogenesis, vascular stabilization, and inflammation. The Wnt pathway is tightly regulated in the adult brain to maintain neurovascular functions. Historically, research in neuroscience has emphasized essentially on investigating the pathway in neurodegenerative disorders. Nonetheless, emerging findings have demonstrated that the pathway is deregulated in vascular- and traumatic-mediated brain injuries. These findings are suggesting that the pathway constitutes a promising target for the development of novel therapeutic protective and restorative interventions. Yet, targeting a complex multifunctional signal transduction pathway remains a major challenge. The review aims to summarize the current knowledge regarding the implication of Wnt pathway in the pathobiology of ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI). Furthermore, the review will present the strategies used so far to manipulate the pathway for therapeutic purposes as to highlight potential future directions.

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