Pellino proteins are a family of evolutionarily conserved ubiquitin ligases involved in intracellular signaling in a wide range of cell types. They are essential for microbe detection and the initiation of innate and adaptive immune responses. Some viruses specifically target the Pellino proteins as part of their immune evasion strategies. Through studies of mouse models of viral infections in the central nervous system, heart, lungs, and skin, the Pellino proteins have been linked to both beneficial and detrimental immune responses. Only in recent years have some of the involved mechanisms been identified. The objective of this review is to highlight the many diverse aspects of viral immunity and pathogenesis that the Pellino proteins have been associated with, in order to promote further research into their functions. After a brief introduction to the cellular signaling mechanisms involving Pellino proteins, their physiological roles in the initiation of immune responses, pathogenesis through excess inflammation, immune regulation, and cell death are presented. Known viral immune evasion strategies are also described. Throughout, areas that require more in-depth investigation are identified. Future research into the functions of the Pellino protein family may reveal fundamental insights into how our immune system works. Such knowledge may be leveraged in the fight against viral infections and their sequala.
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http://dx.doi.org/10.3390/v15071422 | DOI Listing |
Sci Adv
January 2025
Cellular Homeostasis and Recycling, Danish Cancer Institute, DK-2100 Copenhagen, Denmark.
Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).
View Article and Find Full Text PDFAntiviral Res
January 2025
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address:
Enhanced expression of Pellino-1 (Peli1), a ubiquitin ligase is known to be associated with COVID-19 susceptibility. The underlying mechanisms are not known. Here, we report that mice deficient in Peli1 (Peli1) had reduced viral load and attenuated inflammatory immune responses and tissue damage in the lung following SARS-CoV-2 infection.
View Article and Find Full Text PDFHypertension
December 2024
Department of Forensic Medicine (D.L., L.H., Yan Li, Yanfang Yu, Y.S., Youjia Yu, K.L., Z.Z., Y.C., J.W., H.H., F.C.), Nanjing Medical University, China.
Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Medical and Laboratory Genetics Unit, A.O.R.N. "Antonio Cardarelli", 80131 Naples, Italy.
Pulm Pharmacol Ther
December 2024
The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China. Electronic address:
The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells.
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