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OTUD3 is acetylated. 34 / 34
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"These data indicate that CBP linked the glucose and fatty acid overload with OTUD3 acetylation status ( Figure 6 H)."
35675826
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"Acetylation of OTUD3 significantly enhances its activity in forming Lys63 linkages on MAVS, and acetylation can promote ubiquitination of p62 [ xref , xref ]."
38326336
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"As the full activation of OTUD3 may require its acetylation xref , xref , it will be interesting to determine whether OTUD3 acetylation is also involved in PTEN regulation."
36385557
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"We found that OTUD3 acetylation levels were decreased significantly when nine lysine residues were replaced with arginine (9KR) ( Figure S7 J, lane 4 versus lane 3 and lane 2 versus lane 1)."
35675826
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"In metabolism, OTUD3 acetylation promotes its nuclear translocation, where it modulates transcriptional programs related to lipid and glucose homeostasis."
41437362
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"These findings illustrate that OTUD3 sits at the intersection of inflammation and metabolism: inflammatory conditions can alter metabolic gene expression via OTUD3, and conversely, metabolic stressors such as a high-fat diet can modulate OTUD3 acetylation and nuclear translocation [ xref ], affecting inflammatory gene expression."
41437362
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"We further demonstrated that the CBP acetyltransferase, a crucial cofactor in the regulation of energy homeostasis through its acetyltransferase activity, regulates the acetylation and translocation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
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"We found that both glucose and FFA significantly increased OTUD3 acetylation levels in a dose-dependent manner ( Figure 6 C, lanes 2–4 versus lane 1; Figure S7 C, lanes 2–4 versus lane 1)."
35675826
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"OTUD3 is a deubiquitinase dependent on its Lys129-acetylation, and acetylated OTUD3 hydrolyzes polyubiquitination of Lys63 on MAVS during resting state."
37829187
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"ACLY inhibitor SB 204990 remarkably attenuated both glucose- and FFA-stimulated OTUD3 acetylation ( Figures 6 C and S7 C, lanes 6–8 versus lanes 2–4)."
35675826
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"Using acety-Lysine antibody, we confirmed that abundant OTUD3 was acetylated at endogenous level in uninfected macrophages, but not in cells infected with RNA virus ( Figure 5 C)."
32679077
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"We then constructed a series of corresponding OTUD3 point mutants and indeed found that Lys129 was the most critical residue for the acetylation of OTUD3 ( Figure 5 D)."
32679077
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"As GCN5 is one of the most acetyl-CoA-sensitive HATs, we also tested whether OTUD3 acetylation might be GCN5 dependent."
35675826
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"OTUD3 acetylation can also affect its cellular localization."
37829187
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"However, GCN5 failed to increase OTUD3 acetylation levels ( Figure S7 F, lanes 3–6 versus lanes 1 and 2)."
35675826
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"These results demonstrate that high levels of glucose or fatty acids trigger the activation of CBP, leading to increased levels of acetylation of OTUD3, which facilitates its nuclear translocation."
35675826
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"Acetylation regulates OTUD3 localization and activity, whereby acetylated OTUD3 deubiquitinates MAVS to inhibit innate immunity and undergoes nuclear translocation to modulate metabolic gene expression."
41437362
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"The homozygous Lys129R knockin completely abrogated OTUD3 acetylation ( Figure 7 B)."
32679077
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"To know whether OTUD3 acetylation is clinically related, we analyzed acetylation of OTUD3 and IFN-β production in influenza patients."
32679077
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"Interestingly, influenza patients with low levels of OTUD3 acetylation had significantly higher IFN-β production in serum, whereas the patients with higher levels of OTUD3 acetylation showed significa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
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"We demonstrated that in non-infected cells, OTUD3 was acetylated and could actively hydrolyze Lys63-linked ubiquitination of MAVS, thereby repressing MAVS at resting state."
32679077
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"Mechanistically, acetylation of the core OTU domain in OTUD3 markedly enhances deubiquitinase activity on MAVS (mitochondrial antiviral-signaling protein), thereby inhibiting the innate antiviral immune response."
36385557
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"Acetylation of cGAS by KAT5 in its N-terminal domain promotes its DNA-binding ability, increasing the transcription of downstream antiviral genes. xref In addition to the DNA virus infection, acetylation of OTU deubiquitinase 3 (OTUD3) has been verified to be critical to the RNA virus infection. xref Since 2019, SARS-CoV-2 has caused an ongoing pandemic of coronavirus disease 2019 (COVID-19) worldwide. xref Protein acetylation has also been studied in this severe acute respiratory syndrome."
36577755
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"To unambiguously determine the effect of acetylation on OTUD3, we utilized genetic code expansion orthogonal systems ( Neumann et al., 2008 ; Ryu and Schultz, 2006 ) to incorporate acetyl-lysine into [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
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"Enhanced OTUD3 acetylation was observed upon acetyl-CoA treatment ( Figure S7 D, lanes 2–4 versus lane 1)."
35675826
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"To investigate its potential effects on OTUD3 acetylation, CBP was overexpressed in HEK293T cells."
35675826
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"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) ( xref )."
36531510
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"We first sub-cloned OTUD3-WT into pBAD/Myc-His vector and optimized two ribosome binding sites (RBS) to enable efficient expression and purification of the full-length OTUD3 that are non-acetylated (O[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
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"Notably, acetylated OTUD3 plays a restrictive role in early antiviral innate immunity."
41437362
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"OTUD3 acetylation would be removed upon virus infection, and the DUB activity would be blocked."
35283827
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"We show that acetylation of OTUD3 at a single residue, Lys129, in the core OTU domain is necessary for the enzyme activity."
32679077
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"Another prominent example of DUB regulation by post-translational modifications is illustrated by acetylation of OTUD3 in the context of innate immunity surveillance ( xref )."
35764170
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"While OTUD3 acetylation promotes its DUB activity, its deacetylation by SIRT1 inhibits MAVS deubiquitination following viral infection, thus promoting activation of innate immune signaling ( xref )."
35764170
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"We found that OTUD3 was highly acetylated at a number of acetylation sites under 25 mM glucose ( Table S7 )."
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