GADD45A: With or without you.

Autor: Palomer X; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain.; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain.; Pediatric Research Institute-Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain., Salvador JM; Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain., Griñán-Ferré C; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.; Institut de Neurociències, Universitat de Barcelona (NeuroUB), Barcelona, Spain.; Spanish Biomedical Research Center in Neurodegenerative Diseases (CIBERNED)-Instituto de Salud Carlos III, Madrid, Spain., Barroso E; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain.; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain.; Pediatric Research Institute-Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain., Pallàs M; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.; Institut de Neurociències, Universitat de Barcelona (NeuroUB), Barcelona, Spain.; Spanish Biomedical Research Center in Neurodegenerative Diseases (CIBERNED)-Instituto de Salud Carlos III, Madrid, Spain., Vázquez-Carrera M; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain.; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain.; Pediatric Research Institute-Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2024 Jul; Vol. 44 (4), pp. 1375-1403. Date of Electronic Publication: 2024 Jan 24.
DOI: 10.1002/med.22015
Abstrakt: The growth arrest and DNA damage inducible (GADD)45 family includes three small and ubiquitously distributed proteins (GADD45A, GADD45B, and GADD45G) that regulate numerous cellular processes associated with stress signaling and injury response. Here, we provide a comprehensive review of the current literature investigating GADD45A, the first discovered member of the family. We first depict how its levels are regulated by a myriad of genotoxic and non-genotoxic stressors, and through the combined action of intricate transcriptional, posttranscriptional, and even, posttranslational mechanisms. GADD45A is a recognized tumor suppressor and, for this reason, we next summarize its role in cancer, as well as the different mechanisms by which it regulates cell cycle, DNA repair, and apoptosis. Beyond these most well-known actions, GADD45A may also influence catabolic and anabolic pathways in the liver, adipose tissue and skeletal muscle, among others. Not surprisingly, GADD45A may trigger AMP-activated protein kinase activity, a master regulator of metabolism, and is known to act as a transcriptional coregulator of numerous nuclear receptors. GADD45A has also been reported to display a cytoprotective role by regulating inflammation, fibrosis and oxidative stress in several organs and tissues, and is regarded an important contributor for the development of heart failure. Overall data point to that GADD45A may play an important role in metabolic, neurodegenerative and cardiovascular diseases, and also autoimmune-related disorders. Thus, the potential mechanisms by which dysregulation of GADD45A activity may contribute to the progression of these diseases are also reviewed below.
(© 2024 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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