Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 2 of 2

Publication Record

Connections

Control of antiviral innate immune response by protein geranylgeranylation.
Yang S, Harding AT, Sweeney C, Miao D, Swan G, Zhou C, Jiang Z, Fitzgerald KA, Hammer G, Bergo MO, Kroh HK, Lacy DB, Sun C, Glogauer M, Que LG, Heaton NS, Wang D
(2019) Sci Adv 5: eaav7999
MeSH Terms: Adaptor Proteins, Signal Transducing, Alkyl and Aryl Transferases, Animals, Endoplasmic Reticulum, Female, Humans, Immunity, Innate, Macrophages, Alveolar, Male, Mice, Knockout, Neuropeptides, Orthomyxoviridae Infections, Protein Prenylation, Receptor-Interacting Protein Serine-Threonine Kinases, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, rac GTP-Binding Proteins, rac1 GTP-Binding Protein
Show Abstract · Added March 24, 2020
The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates the recruitment of caspase-8 and cFLIP to the MAVS signalosome and the subsequent cleavage of Ripk1 that terminates MAVS signaling. Consistently, mice with myeloid deficiency of protein geranylgeranylation showed improved survival upon influenza A virus infection. Our work revealed a critical role of protein geranylgeranylation in regulating antiviral innate immune response.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
Deger SM, Hung AM, Gamboa JL, Siew ED, Ellis CD, Booker C, Sha F, Li H, Bian A, Stewart TG, Zent R, Mitch WE, Abumrad NN, Ikizler TA
(2017) JCI Insight 2:
MeSH Terms: Adult, Animals, Biomarkers, C-Reactive Protein, Cytokines, Disease Models, Animal, Female, Homeostasis, Humans, Inflammation, Integrin beta1, Kinetics, Male, Mice, Mice, Knockout, Middle Aged, Multivariate Analysis, Muscle Proteins, Muscle, Skeletal, Regression Analysis, Renal Dialysis, Renal Insufficiency, Chronic, SKP Cullin F-Box Protein Ligases, Tripartite Motif Proteins, Ubiquitin-Protein Ligases
Show Abstract · Added March 14, 2018
BACKGROUND - Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients.
METHODS - Whole body and skeletal muscle protein turnover were assessed by stable isotope kinetic studies. We incorporated expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin β1 gene KO CKD mice models.
RESULTS - Among 129 patients with mean (± SD) age 47 ± 12 years, 74% were African American, 73% were male, and 22% had diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP) concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically significant associations between hs-CRP and forearm skeletal muscle protein synthesis, degradation, and net forearm skeletal muscle protein balance (P < 0.001 for all). The associations remained statistically significant after adjustment for clinical and demographic confounders, as well as in sensitivity analysis, excluding patients with diabetes mellitus. In attempting to identify potential mechanisms involved in this correlation, we show increased expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue obtained from an animal model of chronic kidney disease.
CONCLUSION - These data suggest that systemic inflammation is a strong and independent determinant of skeletal muscle protein homeostasis in MHD patients, providing rationale for further studies using anticytokine therapies in patients with underlying systemic inflammation.
FUNDING - This study was in part supported by NIH grants R01 DK45604 and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, the Veterans Administration Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant Program, and the FDA grant 000943.
0 Communities
2 Members
0 Resources
25 MeSH Terms