Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans

ABSTRACT: Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans

PROVIDER: PRJNA1111916 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR29044127_1.fastq.gz	Fastqsanger.gz
	SRR29044127_2.fastq.gz	Fastqsanger.gz
	SRR29044128_1.fastq.gz	Fastqsanger.gz
	SRR29044128_2.fastq.gz	Fastqsanger.gz
	SRR29044133_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 20

Similar Datasets

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans

Project description:IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was unexpectedly partially impaired. Reintroducing wt CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of biallelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding, and suggesting IKKα's role in canonical NF-κB target gene expression in humans.

2024-11-24 | GSE267600 | GEO

Impact of G167R mutation in CHUK gene, coding for IKKα protein, on gene expression in PBMCs

Project description:IKKα is a critical regulator of the non-canonical NF-KB signalling pathway. In patients with combined immunodeficiency, we identified a homozygous missense mutation in CHUK gene, coding for IKKα protein, leading to G167R amino acid change in the kinase domain of the protein. This mutation impairs the kinase activity of IKKα, which results in a range of aberratins in innate and adaptive immunity.

2024-10-09 | GSE256535 | GEO

Omental adipose tissue metaboproteome: differential dysregulation by chronic binge alcohol and ovariectomy in simian immunodeficiency virus-infected female macaques

Project description:Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH). Increased survival and aging of PLWH is associated with increased incidence of at-risk alcohol use and of metabolic comorbidities; and in women, menopause may be an additional factor contributing to metabolic dysregulation, particularly in adipose tissue. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome of simian immunodeficiency virus (SIV) infected macaques. Quantitative discovery-based proteomics identified 1429 differentially expressed proteins. Ingenuity Pathway Analysis calculated z-scores, or activation predictions for a disease or functional pathway. Results revealed functional pathways associated with protein changes centered around the “OmAT metaboproteome profile”. CBA did not affect functional pathways of metabolic disease; but dysregulated proteins involved in AMPK signaling and lipid metabolism. Based on IPA’s calculated z-score, OVX-mediated proteome changes promote pathways associated with glucose and lipid associated metabolic disease. Additionally, OVX was predicted to promote apoptosis, necrosis and reactive oxygen species (ROS) pathways, while CBA was predicted to inhibit these OVX-associated changes. These results provide evidence for the role of ovarian hormone loss in mediating OmAT metaboproteome dysregulation in HIV/SIV and suggest that CBA modifies OVX-associated changes. In the context of OVX, CBA administraton produced larger metabolic and cellular effects; which we speculate may reflect a protective role of estrogen against CBA-mediated adipose tissue injury in female SIV-infected macaques.

2022-08-12 | PXD023076 | Pride

Gut Microbial Dysbiosis Underlies Immune Dysregulation in CVID

Project description:Gut Microbial Dysbiosis Underlies Immune Dysregulation in Common Variable Immunodeficiency

| PRJEB44275 | ENA

Lead-seq: transcriptome-wide in vivo structure probing with lead

Project description:Lead-seq: transcriptome-wide in vivo structure probing with lead

| PRJNA590387 | ENA

IKKα signaling in the nucleus or cytoplasm of keratinocytes leads to opposite skin phenotypes.

Project description:The skin exerts essential roles for the organism survival, such as environmental barrier and immune functions. IKKα is known as an essential protein for skin homeostasis. However, the functions performed by IKKα in the skin and the mechanisms it employs are largely unknown, leading to contradictory interpretations and results regarding the consequences of its deregulation in pathologies such as non-melanoma skin cancer (NMSC). Here, using our previously generated transgenic mouse models which express IKKα in the cytoplasm (C-IKKα mice) or in the nucleus (N-IKKα mice) of basal keratinocytes, we demonstrate that at each subcellular localization, IKKα distinctly regulates signaling pathways important for maintaining the balance between keratinocyte proliferation and differentiation, as well as the inflammatory response of the skin. As a result, N-IKKα mice show an atrophic epidermis with exacerbated terminal differentiation, reminiscent of alterations observed in patients with ichthyosis. Conversely, C-IKKα mice display a hyperplastic epidermis with impaired epidermal differentiation and pustular inflammation, resembling patients with pustular psoriasis. Interestingly, C-IKKα keratinocytes are almost devoid of nuclear IKKα due to endogenous IKKα downregulation. However, these changes in the skin of C-IKKα mice do not lead to the development of squamous cell carcinomas (SCCs), unlike N-IKKα mice, which develop spontaneous SCCs.

2024-11-14 | GSE239533 | GEO

Simian immunodeficiency virus

Project description:Simian immunodeficiency virus Variation

| PRJNA176620 | ENA

Simian immunodeficiency virus

Project description:Simian immunodeficiency virus overview

| PRJNA69627 | ENA

Human immunodeficiency virus

Project description:Human immunodeficiency virus Variation

| PRJNA397463 | ENA

Human immunodeficiency virus

Project description:Human immunodeficiency virus Genome sequencing