Ubiquitin Specific Protease USP48 Destabilizes NF-?B/p65 in Retinal Pigment Epithelium Cells
Por:
Mirra S, Sánchez-Bellver L, Casale C, Pescatore A and Marfany G
Publicada:
1 sep 2022
Ahead of Print:
26 ago 2022
Resumen:
Activation of NF-kappa B transcription factor is strictly regulated to accurately direct cellular processes including inflammation, immunity, and cell survival. In the retina, the modulation of the NF-kappa B pathway is essential to prevent excessive inflammatory responses, which plays a pivotal role in many retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and inherited retinal dystrophies (IRDs). A critical cytokine mediating inflammatory responses in retinal cells is tumor necrosis factor-alpha (TNF alpha), leading to the activation of several transductional pathways, including NF-kappa B. However, the multiple factors orchestrating the appropriate regulation of NF-kappa B in retinal cells still remain unclear. The present study explores how the ubiquitin-specific protease 48 (USP48) downregulation impacts the stability and transcriptional activity of NF-kappa B/p65 in retinal pigment epithelium (RPE), at both basal conditions and following TNF alpha stimulation. We described that USP48 downregulation stabilizes p65. Notably, the accumulation of p65 is mainly detectable in the nuclear compartment and it is accompanied by an increased NF-kappa B transcriptional activity. These results delineate a novel role of USP48 in negatively regulating NF-kappa B in retinal cells, providing new opportunities for therapeutic intervention in retinal pathologies.
Filiaciones:
Mirra S:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
Sánchez-Bellver L:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Casale C:
Institute of Genetics and Biophysics, 'Adriano Buzzati-Traverso' (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
Pescatore A:
Institute of Genetics and Biophysics, 'Adriano Buzzati-Traverso' (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
Marfany G:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
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