Topics

Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma.

08:00 EDT 16th March 2020 | BioPortfolio

Summary of "Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma."

Although the transition metal copper (Cu) is an essential nutrient that is conventionally viewed as a static cofactor within enzyme active sites, a non-traditional role for Cu as a modulator of kinase signalling is emerging. Here, we found that Cu is required for the activity of the autophagic kinases ULK1 and ULK2 (ULK1/2) through a direct Cu-ULK1/2 interaction. Genetic loss of the Cu transporter Ctr1 or mutations in ULK1 that disrupt the binding of Cu reduced ULK1/2-dependent signalling and the formation of autophagosome complexes. Increased levels of intracellular Cu are associated with starvation-induced autophagy and are sufficient to enhance ULK1 kinase activity and, in turn, autophagic flux. The growth and survival of lung tumours driven by KRAS is diminished in the absence of Ctr1, is dependent on ULK1 Cu binding and is associated with reduced levels of autophagy and signalling. These findings suggest a molecular basis for exploiting Cu-chelation therapy to prevent autophagy signalling to limit proliferation and improve patient survival in cancer.

Affiliation

Journal Details

This article was published in the following journal.

Name: Nature cell biology
ISSN: 1476-4679
Pages:

Links

DeepDyve research library

PubMed Articles [12043 Associated PubMed Articles listed on BioPortfolio]

Regulation of lung endothelial permeability by NEK kinases.

Dysregulation of lung endothelial barrier function may lead to lethal outcomes, as demonstrated in the case of the acute respiratory distress syndrome (ARDS). p53 participates in the regulation of the...

Artemisinin attenuated atherosclerosis in high-fat diet-fed ApoE-/- mice by promoting macrophage autophagy via AMPK/mTOR/ULK1 pathway.

Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, anti-oxidant and vascular protection. Recent studies have fou...

Influence of Glutathione on Yeast Fermentation Efficiency under Copper Stress.

Copper in grape musts can influence the fermentation efficiency of during winemaking. The present study revealed the impact of glutathione addition on yeast strains with variable copper sensitivity. ...

Clearing or subverting the enemy: Role of autophagy in protozoan infections.

The protozoan parasites are evolutionarily divergent, unicellular eukaryotic pathogens representing one of the essential sources of parasitic diseases. These parasites significantly affect the economy...

Is there a common drive for buccal movements associated with buccal and lung 'breath' in Lithobates catesbeianus?

In amphibians, there is some evidence that (1) anatomically separate brainstem respiratory oscillators are involved in rhythm generation, one for the buccal rhythm and another for the lung rhythm and ...

Clinical Trials [7595 Associated Clinical Trials listed on BioPortfolio]

Human Biomarkers for Assessing Copper Deficiency

Copper is an essential nutrient for humans and is cofactor in enzymes that participate in critical body functions. Insufficient copper can lead to hematological and neurological abnormali...

A Phase Ib Study of Intravenous Copper Loading With Oral Disulfiram in Metastatic, Castration Resistant Prostate Cancer

The purpose of this study is to determine the safety and optimal dosing of intravenous copper chloride and disulfiram in men with metastatic castrate-resistant prostate cancer (CRPC). Elig...

Immediate vs. Delayed Insertion of Copper T 380A IUD After Termination of Pregnancy Over 12-Weeks Gestation

The purpose of this study is to compare delayed vs. immediate insertion of the Copper T 380 IUD after termination of pregnancy after 12 weeks.

IMPACT STUDY: Investigating Microbial Pathogen Activity of Copper Textiles

The purpose of this study is to assess the impact of copper linens on hospital acquired infections and drug resistant bacteria.

Study of Anlotinib Hydrochloride Capsule in Subjects With Small Cell Lung Cancer

Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor-associated kinases i...

Medical and Biotech [MESH] Definitions

P-type ATPases which transport copper ions across membranes in prokaryotic and eukaryotic cells. They possess a conserved CYSTEINE-HISTIDINE-SERINE (CPx) amino acid motif within their transmembrane helices that functions in cation translocation and catalytic activation, and an N-terminal copper-binding CxxC motif that regulates enzyme activity. They play essential roles in intracellular copper homeostasis through regulating the uptake, efflux and storage of copper ions, and in cuproprotein biosynthesis.

An adaptor protein component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 that forms stoichiometric complexes with TOR KINASES, which it negatively regulates. It functions as a positive regulator of RIBOSOMAL PROTEIN S6 KINASES.

Unstable isotopes of copper that decay or disintegrate emitting radiation. Cu atoms with atomic weights 58-62, 64, and 66-68 are radioactive copper isotopes.

A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response.

A multi-copper blood FERROXIDASE involved in iron and copper homeostasis and inflammation.

Quick Search


DeepDyve research library

Relevant Topics

Pulmonary
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Enzymes
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...


Searches Linking to this Article