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Article ; Online: Alphabetti kinase Spaghetti: the complex roles of IKKα and β in the canonical NF-κB pathway.

Perkins, Neil D

2022 Volume 479, Issue 11, Page(s) 1121–1126

Abstract: Numerous studies, published over many years, have established the key role that the IκB kinase (IKK) subunits, α and β, play in regulating the Nuclear Factor κB (NF-κB) pathway. This research generally concluded that their functions can be separated, ... ...

Abstract	Numerous studies, published over many years, have established the key role that the IκB kinase (IKK) subunits, α and β, play in regulating the Nuclear Factor κB (NF-κB) pathway. This research generally concluded that their functions can be separated, with IKKβ being the critical regulator of the canonical NF-κB pathway, while IKKα functions as the key activating kinase for the non-canonical pathway. However, other roles for these kinases have been described and several reports concluded that this separation of their functions may not always be the case. This commentary discusses the recent report by Biochem J. 479, 305-325, who elegantly demonstrate that in KRAS driven colorectal cancer cell lines, IKKα is an important regulator of the canonical NF-κB pathway. As is so often the case with trying to understand the complexity of NF-κB signalling, cellular context is everything.
MeSH term(s)	Cell Line ; I-kappa B Kinase/genetics ; I-kappa B Kinase/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Protein Serine-Threonine Kinases ; Signal Transduction
Chemical Substances	NF-kappa B ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2022-05-28
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BCJ20220023
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Article ; Online: More than just an IκB kinase: the IKK complex coordinates mRNA stability and transcription.

Perkins, Neil D

The EMBO journal

2018 Volume 37, Issue 24

MeSH term(s)	I-kappa B Kinase ; Phosphorylation ; RNA Stability
Chemical Substances	I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2018-12-03
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2018101084
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Article ; Online: The importance of the p50 NF-κB subunit.

Perkins, Neil D

Cell cycle (Georgetown, Tex.)

2015 Volume 14, Issue 18, Page(s) 2877–2878

MeSH term(s)	DNA Replication/physiology ; Genomic Instability/physiology ; Humans ; NF-kappa B p50 Subunit/metabolism ; S Phase/physiology
Chemical Substances	NF-kappa B p50 Subunit
Language	English
Publishing date	2015-08-20
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2015.1010952
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Article ; Online: Hypoxia induces rapid, STAT3 and ROS dependent, mitochondrial translocation of RelA(p65) and IκBα.

Ivanova, Iglika G / Perkins, Neil D

Bioscience reports

2019 Volume 39, Issue 9

Abstract: The nuclear factor-κB (NF-κB) family of transcription factors can directly or indirectly regulate many important areas of biology, including immunity, inflammation and cell survival. One intriguing aspect of NF-κB crosstalk with other cell signalling ... ...

Abstract	The nuclear factor-κB (NF-κB) family of transcription factors can directly or indirectly regulate many important areas of biology, including immunity, inflammation and cell survival. One intriguing aspect of NF-κB crosstalk with other cell signalling pathways is its regulation of mitochondrial biology, including biogenesis, metabolism and apoptosis. In addition to regulating the expression of mitochondrial genes encoded in the nucleus, NF-κB signalling components are also found within mitochondria themselves and associated with mitochondrial DNA. However, complete biochemical analysis of mitochondrial and sub-mitochondrial localisation of all NF-κB subunits has not been undertaken. Here, we show that only the RelA NF-κB subunit and its inhibitor IκBα reside within mitochondria, whilst p50 is found in the endoplasmic reticulum (ER). Fractionation of mitochondria revealed that only RelA was found in the mitoplast, the location of the mtDNA. We demonstrate that hypoxia leads to a very rapid but transient accumulation of RelA and IκBα in mitochondria. This effect required reactive oxygen species (ROS) but was not dependent on the hypoxia sensing transcription factor subunit HIF1α or intracellular Ca
MeSH term(s)	Calcium/metabolism ; Cell Hypoxia/genetics ; DNA, Mitochondrial/genetics ; Endoplasmic Reticulum/genetics ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; MCF-7 Cells ; Mitochondria/genetics ; Mitochondria/metabolism ; NF-KappaB Inhibitor alpha/genetics ; NF-kappa B/genetics ; Reactive Oxygen Species/metabolism ; STAT3 Transcription Factor/genetics ; Transcription Factor RelA/genetics
Chemical Substances	DNA, Mitochondrial ; HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; NF-kappa B ; RELA protein, human ; Reactive Oxygen Species ; STAT3 Transcription Factor ; Transcription Factor RelA ; NF-KappaB Inhibitor alpha (139874-52-5) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20192101
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Article ; Online: Pregnant women's attitudes and behaviours towards antenatal vaccination against Influenza and COVID-19 in the Liverpool City Region, United Kingdom: Cross-sectional survey.

Kilada, Samantha / French, Neil / Perkins, Elizabeth / Hungerford, Dan

Vaccine: X

2023 Volume 15, Page(s) 100387

Abstract: Objectives: Influenza poses a serious health risk to pregnant women and their babies. Despite this risk, influenza vaccine uptake in pregnant women in the UK is less than 50%. Little is known about how COVID-19 affects pregnant women, but its management ...

Abstract	Objectives: Influenza poses a serious health risk to pregnant women and their babies. Despite this risk, influenza vaccine uptake in pregnant women in the UK is less than 50%. Little is known about how COVID-19 affects pregnant women, but its management may affect attitudes and behaviours towards vaccination in pregnancy. The study objectives were to establish attitudes and knowledge of pregnant women towards influenza disease and influenza vaccination and to compare these to attitudes and knowledge about COVID-19 and COVID-19 vaccination. Design: A cross-sectional survey was conducted using an online questionnaire distributed through local advertisement and social media outlets. Information was sought on attitudes and knowledge of influenza and COVID-19 and their respective vaccines. Participants and setting: Pregnant women residing in Liverpool City Region, UK. Results: Of the 237 respondents, 73.8% reported receiving an influenza vaccine. Over half (56.5%) perceived themselves to be at risk from influenza, 70.5% believed that if they got influenza, their baby would get ill, and 64.6% believed getting influenza could hurt their baby, 60.3% believed that the influenza vaccine would prevent their baby from getting ill, and 70.8% believed it would protect their baby. Only 32.9% of respondents stated they would receive the COVID-19 vaccine if it were available to them. However, 80.2% stated they would receive a COVID-19 vaccine if they were not pregnant. Most of the women stated that they would accept a vaccine if recommended to them by healthcare professionals. Conclusions: Acceptance of the influenza and COVID-19 vaccines during pregnancy seems to be more related to the safety of the baby rather than the mother. Women perceived their child to be more at risk than themselves. Information about influenza and COVID-19 vaccine safety as well as healthcare provider recommendations play an important role in vaccine uptake in pregnant women.
Language	English
Publishing date	2023-09-16
Publishing country	England
Document type	Journal Article
ISSN	2590-1362
ISSN (online)	2590-1362
DOI	10.1016/j.jvacx.2023.100387
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Article ; Online: Increased migration and motility in XIAP-null cells mediated by the C-RAF protein kinase.

Russell, Lauren G / Davis, Lydia A K / Hunter, Jill E / Perkins, Neil D / Kenneth, Niall S

Scientific reports

2022 Volume 12, Issue 1, Page(s) 7943

Abstract: The product encoded by the X-linked inhibitor of apoptosis (XIAP) gene is a multi-functional protein which not only controls caspase-dependent cell death, but also participates in inflammatory signalling, copper homeostasis, response to hypoxia and ... ...

Abstract	The product encoded by the X-linked inhibitor of apoptosis (XIAP) gene is a multi-functional protein which not only controls caspase-dependent cell death, but also participates in inflammatory signalling, copper homeostasis, response to hypoxia and control of cell migration. Deregulation of XIAP, either by elevated expression or inherited genetic deletion, is associated with several human disease states. Reconciling XIAP-dependent signalling pathways with its role in disease progression is essential to understand how XIAP promotes the progression of human pathologies. In this study we have created a panel of genetically modified XIAP-null cell lines using TALENs and CRISPR/Cas9 to investigate the functional outcome of XIAP deletion. Surprisingly, in our genetically modified cells XIAP deletion had no effect on programmed cell death, but instead the primary phenotype we observed was a profound increase in cell migration rates. Furthermore, we found that XIAP-dependent suppression of cell migration was dependent on XIAPdependent control of C-RAF levels, a protein kinase which controls cell signalling pathways that regulate the cytoskeleton. These results suggest that XIAP is not necessary for control of the apoptotic signalling cascade, however it does have a critical role in controlling cell migration and motility that cannot be compensated for in XIAP-knockout cells.
MeSH term(s)	Apoptosis ; Caspases/metabolism ; Lymphocytes, Null/metabolism ; Proto-Oncogene Proteins c-raf/metabolism ; Signal Transduction ; X-Linked Inhibitor of Apoptosis Protein/metabolism
Chemical Substances	X-Linked Inhibitor of Apoptosis Protein ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2022-05-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-11438-8
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Article ; Online: Emerging from NF-κB's shadow, SUMOylated IκBα represses transcription.

Perkins, Neil D

Cancer cell

2013 Volume 24, Issue 2, Page(s) 139–140

Abstract: In this issue of Cancer Cell, Mulero and colleagues describe an NF-κB independent transcriptional repression function for SUMOylated IκBα. This compelling and provocative model links IκBα to the activity of the Polycomb repressors and provides a ... ...

Abstract	In this issue of Cancer Cell, Mulero and colleagues describe an NF-κB independent transcriptional repression function for SUMOylated IκBα. This compelling and provocative model links IκBα to the activity of the Polycomb repressors and provides a mechanism to link inflammatory signaling to skin homeostasis.
MeSH term(s)	Animals ; Chromatin/metabolism ; Humans ; I-kappa B Proteins/metabolism ; NF-KappaB Inhibitor alpha ; Skin Neoplasms/metabolism
Chemical Substances	Chromatin ; I-kappa B Proteins ; NFKBIA protein, human ; NF-KappaB Inhibitor alpha (139874-52-5)
Language	English
Publishing date	2013-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccr.2013.07.011
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Article ; Online: Cysteine 38 holds the key to NF-κB activation.

Perkins, Neil D

Molecular cell

2012 Volume 45, Issue 1, Page(s) 1–3

Abstract: The importance of parallel signaling pathways controlling NF-κB subunit posttranslational modifications is demonstrated by Sen et al. (2012), who reveal that RelA (p65) sulfhydration, at its highly conserved cysteine 38 residue, regulates association ... ...

Abstract	The importance of parallel signaling pathways controlling NF-κB subunit posttranslational modifications is demonstrated by Sen et al. (2012), who reveal that RelA (p65) sulfhydration, at its highly conserved cysteine 38 residue, regulates association with the coactivator RPS3, DNA binding, and antiapoptotic gene expression.
Language	English
Publishing date	2012-01-13
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2011.12.023
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Article ; Online: The diverse and complex roles of NF-κB subunits in cancer.

Perkins, Neil D

Nature reviews. Cancer

2012 Volume 12, Issue 2, Page(s) 121–132

Abstract: It is only recently that the full importance of nuclear factor-κB (NF-κB) signalling to cancer development has been understood. Although much attention has focused on the upstream pathways leading to NF-κB activation, it is now becoming clear that the ... ...

Abstract	It is only recently that the full importance of nuclear factor-κB (NF-κB) signalling to cancer development has been understood. Although much attention has focused on the upstream pathways leading to NF-κB activation, it is now becoming clear that the inhibitor of NF-κB kinases (IKKs), which regulate NF-κB activation, have many independent functions in tissue homeostasis and normal immune function that could compromise the clinical utility of IKK inhibitors. Therefore, if the NF-κB pathway is to be properly exploited as a target for both anticancer and anti-inflammatory drugs, it is appropriate to reconsider the complex roles of the individual NF-κB subunits.
MeSH term(s)	Genes, Tumor Suppressor ; Humans ; NF-kappa B/chemistry ; NF-kappa B/physiology ; Neoplasms/physiopathology
Chemical Substances	NF-kappa B
Language	English
Publishing date	2012-01-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc3204
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Zs.MG 24: Show issues

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Article ; Online: A Cell-Based Optimised Approach for Rapid and Efficient Gene Editing of Human Pluripotent Stem Cells.

Cuevas-Ocaña, Sara / Yang, Jin Ye / Aushev, Magomet / Schlossmacher, George / Bear, Christine E / Hannan, Nicholas R F / Perkins, Neil D / Rossant, Janet / Wong, Amy P / Gray, Michael A

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Introducing or correcting disease-causing mutations through genome editing in human pluripotent stem cells (hPSCs) followed by tissue-specific differentiation provide sustainable models of multiorgan diseases, such as cystic fibrosis (CF). However, low ... ...

Abstract	Introducing or correcting disease-causing mutations through genome editing in human pluripotent stem cells (hPSCs) followed by tissue-specific differentiation provide sustainable models of multiorgan diseases, such as cystic fibrosis (CF). However, low editing efficiency resulting in extended cell culture periods and the use of specialised equipment for fluorescence activated cell sorting (FACS) make hPSC genome editing still challenging. We aimed to investigate whether a combination of cell cycle synchronisation, single-stranded oligodeoxyribonucleotides, transient selection, manual clonal isolation, and rapid screening can improve the generation of correctly modified hPSCs. Here, we introduced the most common CF mutation, ΔF508, into the
MeSH term(s)	Humans ; Gene Editing/methods ; CRISPR-Cas Systems/genetics ; Pluripotent Stem Cells/metabolism ; Mutation ; Heterozygote
Language	English
Publishing date	2023-06-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241210266
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