Copper is a potent inhibitor of both the canonical and non-canonical NFκB pathways

Kenneth, Niall S.; Hucks, George E; Kocab, Andrew J.; McCollom, Annie L; Duckett, Colin S.

doi:10.4161/cc.27922

Cited by 25 publications

(18 citation statements)

References 41 publications

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“…As depicted schematically in Figure 3A , Karpas 299 cells were treated with SM or exposed to CD30L, incubated with bromouridine, and the bromouridine-labeled RNA was isolated and converted into cDNA libraries for deep sequencing. In the initial analysis of the Bru-seq data, we compared the expression of two well-characterized NF-κB gene targets: BIRC3 , which encodes the c-IAP2 protein, and NFKBIA , the gene encoding IκBα ( 11 , 20 , 22 ). The profiles of the mapped sequencing reads were similar for both stimuli ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling

et al. 2015

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Cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2) play central roles in signal transduction mediated by numerous receptors that participate in inflammatory and immune responses. In certain pathways, such as activation of NF-κB, their degradation is a major regulatory event and is physiologically induced by activation of receptors. Additionally, a number of synthetic compounds have been developed that also target the c-IAPs and induce their degradation. However, the extent of a synthetic IAP antagonist's ability to mirror the transcriptional program by a physiological signal remains unclear. Here we take a systems approach to compare the transcriptional programs triggered by activation of CD30, a well-characterized receptor previously shown to induce the degradation of the c-IAPs, to SM-164, a synthetic IAP antagonist that specifically triggers c-IAP degradation. Employing a technique that allows the specific analysis of newly transcribed RNA, we have generated comparative transcriptome profiles for CD30 activation and SM-164 treatment. Analysis of these profiles revealed that the genes regulated by each stimulus were not completely shared, indicating novel functions of IAP antagonists and consequences of c-IAP1/2 degradation. The data identified a role for c-IAP1/2 in the regulation of the ribosome and protein synthesis, which was subsequently confirmed by biological assays. These findings expand our knowledge of the roles of c-IAP1/2 in signaling and provide insight into the mechanism of synthetic IAP antagonists, furthering our understanding of their therapeutic potential.

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Section: Resultsmentioning

confidence: 99%

“…The cell suspension was then divided into tubes, and whole cell lysates and nuclear extracts were subsequently prepared. Whole cell lysates were prepared using RIPA lysis buffer in a process that has been described previously ( 22 ). Nuclear extracts were prepared from the cells as described before ( 39 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling

et al. 2015

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“…Various anti-inflammatory drugs could be used as a supplement to scavenge ROS and hence improve the survival span of several types of cells (61). Antioxidants also act as inhibitors of radical production processes by removing harmful ROS formed during normal cellular metabolism (62,63). It is known that the polyphenolic natural antioxidant resveratrol, present in red wine and grapes, exhibits a number of pharmacological effects including anti-inflammation, antioxidation, anti-apoptosis, subsequently promoting longevity (64,65).…”

Section: Diet May Contribute To Longevity By Enhancing the Pink1 Signmentioning

confidence: 99%

PINK1 signaling in mitochondrial homeostasis and in aging (Review)

Nakano

Ogino

Ichimura

et al. 2016

International Journal of Molecular Medicine

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Mitochondrial dysfunction is involved in the pathology of Parkinson's disease, an age-associated neurodegenerative disorder. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is responsible for the most common form of recessive Parkinson's disease. PINK1 is a mitochondrial kinase that is involved in mitrochondrial quality control and promotes cell survival. PINK1 has been shown to protect against neuronal cell death induced by oxidative stress. Accordingly, PINK1 deficiency is associated with mitochondrial dysfunction as well as increased oxidative cellular stress and subsequent neuronal cell death. In addition, several mitochondrial chaperone proteins have been shown to be substrates of the PINK1 kinase. In this review, we discuss recent studies concerning the signaling cascades and molecular mechanisms involved in the process of mitophagy, which is implicated in neurodegeneration and in related aging associated with oxidative stress. Particular attention will be given to the molecular mechanisms proposed to explain the effects of natural compounds and/or food ingredients against oxidative stress. Knowledge of the molecular mechanisms involved in this cellular protection could be critical for developing treatments to prevent and control excessive progression of neurodegenerative disorders.

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“…Cu influences several molecular pathways that induce a pro-angiogenic response, 13 including direct binding to, and promoting the expression of, angiogenic factors. 14,15 Cu also influences the ability of cancerous cells to metastasize through activation of metabolic and proliferative enzymes. 11 For example, LOX is secreted by cancer cells to create a pro-metastatic niche.…”

Section: Introductionmentioning

confidence: 99%

Defining the human copper proteome and analysis of its expression variation in cancers

et al. 2017

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Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.

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Copper is a potent inhibitor of both the canonical and non-canonical NFκB pathways

Cited by 25 publications

References 41 publications

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling

PINK1 signaling in mitochondrial homeostasis and in aging (Review)

Defining the human copper proteome and analysis of its expression variation in cancers

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