G protein coupled receptor kinase 5 modifies the nucleolar stress response activated by actinomycin D.
Biochem Cell Biol
; 99(4): 508-518, 2021 08.
Article
en En
| MEDLINE
| ID: mdl-33507833
ABSTRACT
G protein coupled receptor kinase 5 (GRK5) is localized within the nucleus and moderates functions such as DNA transcription, in addition to its localization at the plasma membrane. In this report, we show that GRK5 modifies the nucleolar stress response activated by the DNA polymerase inhibitor, actinomycin D (ActD). We show an increased sensitivity to the apoptotic effects of ActD on cervical HeLa cells and the breast cancer cell line MDA MB 231 with reduced protein expression of GRK5. We also tested two types of breast cancer cells (MDA MB 231 and MCF7 cells) and found that the rate of response to ActD varied between them because they have innate differences in the protein expression of GRK5. We also found that GRK5 phosphorylates nucleophosmin (NPM1) at T199 before and during the early stages of ActD treatment. Phosphorylation at T199 increases the ability of NPM1 to interact with p14ARF in vitro, which may affect the protein expression levels of p14ARF. We found that the expression levels of p14ARF were lower in the cells transfected with the control shRNA, but higher in cells transfected with GRK5 shRNA. Collectively, this suggests that GRK5 modifies the nucleolar stress response associated with ActD.
Palabras clave
G protein coupled receptor (GPCR); G protein coupled receptor kinase (GRK); actinomycin D (ActD); actinomycine D (ActD); kinase associée au récepteur couplé à la protéine G (GRK); nucleolar stress response; nucleophosmin (NPM1); nucléophosmine (NPM1); récepteur couplé à la protéine G (RCPG); réponse au stress nucléolaire
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Nucléolo Celular
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Dactinomicina
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Quinasa 5 del Receptor Acoplado a Proteína-G
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Antibióticos Antineoplásicos
/
Neoplasias
Idioma:
En
Revista:
Biochem Cell Biol
Asunto de la revista:
BIOQUIMICA
Año:
2021
Tipo del documento:
Article