Phenotypic screen identifies JAK2 as a major regulator of FAT10 expression.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Phenotypic screen identifies JAK2 as a major regulator of FAT10 expression."

FAT10 is a ubiquitin-like protein suggested to target proteins for proteasomal degradation. It is highly upregulated upon pro-inflammatory cytokines namely TNFα, IFNγ and IL6, and was found to be highly expressed in various epithelial cancers. Evidence suggests that FAT10 is involved in cancer development and may have a pro- tumorigenic role. However, its biological role is still unclear as is its biochemical and cellular regulation. To identify pathways underlying FAT10 expression in the context of pro-inflammatory stimulation, which characterizes the cancerous environment, we implemented a phenotypic transcriptional reporter screen with a library of annotated compounds. We identified AZ960, a potent JAK2 inhibitor, which significantly downregulates FAT10 under pro-inflammatory cytokines, in an NFκB-independent manner. We validated JAK2 as a major regulator of FAT10 expression via knockdown, and suggest that the transcriptional effects are mediated through pSTAT1/3/5. Overall, we elucidated a pathway regulating FAT10 transcription and discovered a tool compound to chemically downregulate FAT10 expression, and further study its biology.


Journal Details

This article was published in the following journal.

Name: ACS chemical biology
ISSN: 1554-8937


DeepDyve research library

PubMed Articles [18728 Associated PubMed Articles listed on BioPortfolio]

IFNγ potentiates TNFα/TNFR1 signaling to induce FAT10 expression in macrophages.

The tight regulation of the cytokine network during macrophage activation is of prime importance to enable a fast and potent innate immune response against exogenous pathogens. The inflammation mediat...

Attenuation of the Innate Immune Response against Viral Infection Due to ZNF598-Promoted Binding of FAT10 to RIG-I.

Excessive innate immune response is harmful to the host, and aberrant activation of the cytoplasmic viral RNA sensors RIG-I and MDA5 leads to autoimmune disorders. ZNF598 is an E3 ubiquitin ligase inv...

mA methylation modulates adipogenesis through JAK2-STAT3-C/EBPβ signaling.

N-methyladenosine (mA), the most abundant internal mRNA modification in eukaryotes, plays a vital role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Here, we r...

JAK2 and PTPRC mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

In this study, we aimed to explore the expression levels of JAK2 and PTPRC in peripheral blood mononuclear cells (PBMCs) from SLE patients and controls, detect the effects of SLE activity on genes mRN...

Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma.

Copy number alterations (CNAs) of 9p24.1 occur frequently in Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), primary central nervous system lymphoma, and primary testicular lympho...

Clinical Trials [5222 Associated Clinical Trials listed on BioPortfolio]

Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases cha...

Dual PD-1 and JAK2 Inhibition in Hematological Malignancies

Pembrolizumab will have significant clinical activity in patients with Intermediate and high risk MF, advanced PV who have been resistant, failed or are intolerant to JAK2 inhibitor therap...

A Study of the Efficacy of MK-0683 in Patients With Polycythaemia Vera and Essential Thrombocythaemia

The aim of the present study is to evaluate the efficacy and safety of MK-0683 in the treatment of PV and ET. This agent has most recently been shown to be a potent inhibitor of the autono...

Expression of Erythroid Differentiation Regulator 1 (Erdr1) in Vitiligo

Expression of Erythroid differentiation regulator 1 (Erdr1) cytokine in vitiligo

Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS)

Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregat...

Medical and Biotech [MESH] Definitions

A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.

A DNA binding protein, transcriptional regulator, and proto-oncogene protein that contains 10 CYS2-HIS2 ZINC FINGERS. It functions as a positive or negative regulator of expression for target genes involved in organism development.

A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage.

Screens which absorb the energy in the x-ray beam that has penetrated the patient and convert this energy into a light pattern which has as nearly as possible the same information as the original x-ray beam. The more light a screen produces for a given input of x-radiation, the less x-ray exposure and thus shorter exposure time are needed to expose the film. In most film-screen systems, the film is sandwiched between two screens in a cassette so that the emulsion on each side is exposed to the light from its contiguous screen.

The capability of an organism to survive and reproduce. The phenotypic expression of the genotype in a particular environment determines how genetically fit an organism will be.

Quick Search

DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...

Searches Linking to this Article