G Protein-Coupled Receptor Systems as Crucial Regulators of DNA Damage Response Processes

International Journal of Molecular Sciences

Hanne Leysen¹  Stuart Maudsley¹  JhanaO. Hendrickx¹  Bronwen Martin¹  Jaana van Gastel¹  Paula Santos-Otte² 

[1] Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium;Institute of Biophysics, Humboldt-Universität zu Berlin, 10115 Berlin, Germany;

关键词: G protein-coupled receptor (GPCR);    aging;    DNA damage;    β-arrestin;    G protein-coupled receptor kinase (GRK);    interactome;    G protein-coupled receptor kinase interacting protein 2 (GIT2);    ataxia telangiectasia mutated (ATM);    clock proteins;    energy metabolism;   

DOI  :  10.3390/ijms19102919

来源: DOAJ

【 摘 要 】

G protein-coupled receptors (GPCRs) and their associated proteins represent one of the most diverse cellular signaling systems involved in both physiological and pathophysiological processes. Aging represents perhaps the most complex biological process in humans and involves a progressive degradation of systemic integrity and physiological resilience. This is in part mediated by age-related aberrations in energy metabolism, mitochondrial function, protein folding and sorting, inflammatory activity and genomic stability. Indeed, an increased rate of unrepaired DNA damage is considered to be one of the ‘hallmarks’ of aging. Over the last two decades our appreciation of the complexity of GPCR signaling systems has expanded their functional signaling repertoire. One such example of this is the incipient role of GPCRs and GPCR-interacting proteins in DNA damage and repair mechanisms. Emerging data now suggest that GPCRs could function as stress sensors for intracellular damage, e.g., oxidative stress. Given this role of GPCRs in the DNA damage response process, coupled to the effective history of drug targeting of these receptors, this suggests that one important future activity of GPCR therapeutics is the rational control of DNA damage repair systems.

【 授权许可】

Unknown