Is ATP the Only Nucleoside Triphosphate among ATP, CTP, GTP, and UTP to Have a Role in Kinase Catalysis of Heme-Regulated Inhibitor toward eIF2α during Lung Cancer Development?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F23%3A10464325" target="_blank" >RIV/00216208:11310/23:10464325 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=l6Snp8rwT2" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=l6Snp8rwT2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/catal13020281" target="_blank" >10.3390/catal13020281</a>

Result language

angličtina

Original language name

Is ATP the Only Nucleoside Triphosphate among ATP, CTP, GTP, and UTP to Have a Role in Kinase Catalysis of Heme-Regulated Inhibitor toward eIF2α during Lung Cancer Development?

Original language description

The heme-regulated eukaryotic initiation factor 2 alpha (eIF2α) kinase, also known as heme-regulated inhibitor (HRI), detects misfolded proteins and induces cytoprotective response to stress, mainly caused by heme-shortage. The nucleoside triphosphate ATP serves as the main donor of phosphate for the phosphorylation of eIF2α by HRI in human cells. However, the other main nucleoside triphosphates (CTP, GTP, UTP) are also present at relatively high concentrations, especially in human tumor cells. Therefore, in this short communication we evaluate the role of four substrates (namely ATP, CTP, GTP, and UTP) on human HRI kinase activity. Additionally, for the first time, we perform a detailed kinetics study of the HRI G202S mutant, whose presence in the human lung is associated with cancer development. Here, the role of all four tested nucleoside triphosphates during cancer development is discussed from the point of view of the HRI activity. The results showed that the kcat value of GTP was lower than that of ATP but was significantly higher than those of CTP and UTP. Additionally, the kcat value of GTP for G202S was approximately 20% higher than that for wild-type, while the kcat values of ATP, CTP, and UTP for G202S were lower than those for wild-type.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/8F20011" target="_blank" >8F20011: Prevention of antibiotic resistance by TARGEted Treatment of pneumonia in children</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Catalysts

ISSN

2073-4344

e-ISSN

2073-4344

Volume of the periodical

13

Issue of the periodical within the volume

2

Country of publishing house

CH - SWITZERLAND

Number of pages

12

Pages from-to

281

UT code for WoS article

000939323700001

EID of the result in the Scopus database

2-s2.0-85148863790