IndraLab

Statements

USP29 binds cGAS. 23 / 23
| 23
sparser
"Because USP29 interacted with cGAS and was upregulated by HSV-1 infection, we investigated its role in regulating HSV-1- or cytoplasmic DNA-triggered innate immune signaling."
32457395
sparser
"39,42 Because USP29 interacted with cGAS and was upregulated by HSV-1 infection, we investigated its role in regulating HSV-1- or cytoplasmic DNA-triggered innate immune signaling."
32457395
sparser
"Interestingly, we found that TRIM38 constitutively interacts with cGAS but not with USP29, whereas USP29 constitutively interacts with cGAS but not with TRIM38 (Supplementary information, Fig.  xref ), indicating that TRIM38 and USP29 independently interacts with and regulates cGAS."
32457395
sparser
"Together, these data suggest that USP29 interacts with cGAS directly and constitutively in resting cells and after HSV-1 infection."
32457395
sparser
"Domain mapping analysis showed that the ubiquitin carboxyl-terminal hydrolase (UCH) domain of USP29 and the C-terminal domain containing the nucleotidyltransferase (NTase) domain of cGAS were responsible for USP29-cGAS association (Fig.  xref )."
32457395
sparser
"c Proximity ligation assay (PLA) and confocal microscopy imaging of cGAS and USP29 interaction in MEFs that were left uninfected (Mock) or infected with HSV-1 for 4 h (left images)."
32457395
sparser
"It has been proposed that three pools of cGAS exist in uninfected cells: unmodified, Lys217-sumoylated and constitutively Lys271-ubiquitinated cGAS. xref Sumoylation at Lys217 antagonizes K48-linked ubiquitination of Lys271 of cGAS, thereby inhibiting its proteasomal degradation. xref In our study, we found that USP29 constitutively interacted with cGAS and USP29 deficiency substantially potentiated basal K48-linked ubiquitination of cGAS and downregulated cGAS protein level without affecting its mRNA expression in uninfected cells, indicating that USP29 constitutively removes K48-linked ubiquitination of cGAS to maintain a relatively high level of cGAS under steady conditions."
32457395
sparser
"In addition, USP29 selectively interacted with cGAS but not with other molecules including MITA, RIG-I, MAVS, TBK1 or IRF3 (Supplementary information, Fig.  xref )."
32457395
sparser
"USP29 deubiquitinates cGAS in the presence or absence of HSV-1 infection Because USP29 interacts with cGAS and its enzyme activity is required for regulating antiviral signaling, we investigated b ELISA analysis of IFN-β, IFN-α, TNF, and CCL5 in the supernatants of Usp29 +/+ and Usp29 m/m BMDMs infected with HSV-1 for 0-24 h, or mock transfected (Mock) or transfected with DNA90, HSV60 or HSV120 for 12 h."
32457395
sparser
"Previous studies have demonstrated that accumulation of dsDNA in the cytoplasm induces micronuclei-localization of cGAS. xref , xref , xref In our study, we found that a portion of USP29-cGAS associating spots were localized at perinuclear compartments after HSV-1 infection."
32457395
sparser
"Although the nature of such subcellular compartments is unclear, the localization of cGAS might also play a role for increased USP29-cGAS association after HSV-1 infection."
32457395
sparser
"USP29 interacts with cGAS."
32457395
sparser
"Our results suggest that HSV-1 infection upregulated USP29, which might be responsible for increased USP29-cGAS association after HSV-1 infection."
32457395
sparser
"Mechanistically, USP29 constitutively interacts with cGAS, deconjugates K48-linked polyubiquitin chains from cGAS and stabilizes cGAS in uninfected cells or after HSV-1 infection."
32457395
sparser
"39, 42 USP29 promotes HSV-1-triggered innate antiviral signaling in THP-1 cells Because USP29 interacted with cGAS and was upregulated by HSV-1 infection, we investigated its role in regulating HSV-1-or cytoplasmic DNA-triggered innate immune signaling."
32457395
sparser
"Domain mapping analysis showed that the ubiquitin carboxyl-terminal hydrolase (UCH) domain of USP29 and the C-terminal domain containing the nucleotidyltransferase (NTase) domain of cGAS were responsible for USP29-cGAS association (Fig. 1d, e)."
32457395
sparser
"USP29 constitutively interacts with cGAS and deconjugates K48-linked polyubiquitin chains from cGAS in the absence or presence of HSV-1 infection, which stabilizes cGAS and promotes cGAS-mediated cellular antiviral responses."
32457395
sparser
"Results from endogenous immunoprecipitation assays suggested that USP29 constitutively interacted with cGAS in bone marrow-derived macrophages (BMDMs), bone marrow-derived dendritic cells (BMDCs), mouse embryonic fibroblasts (MEFs), mouse lung fibroblasts (MLFs) or human monocytic THP-1 cells and their association was potentiated after HSV-1 infection (Fig. 1b and Supplementary information, Fig. S2e)."
32457395
sparser
"In addition, USP29 selectively interacted with cGAS but not with other molecules including MITA, RIG-I, MAVS, TBK1 or IRF3 (Supplementary information, Fig. S2d)."
32457395
sparser
"Results from endogenous immunoprecipitation assays suggested that USP29 constitutively interacted with cGAS in bone marrow-derived macrophages (BMDMs), bone marrow-derived dendritic cells (BMDCs), mouse embryonic fibroblasts (MEFs), mouse lung fibroblasts (MLFs) or human monocytic THP-1 cells and their association was potentiated after HSV-1 infection (Fig.  xref and Supplementary information, Fig.  xref )."
32457395
sparser
"Because USP29 interacts with cGAS and its enzyme activity is required for regulating antiviral signaling, we investigated whether USP29 eliminated polyubiquitin chains from cGAS."
32457395
sparser
"Interestingly, we found that TRIM38 constitutively interacts with cGAS but not with USP29, whereas USP29 constitutively interacts with cGAS but not with TRIM38 (Supplementary information, Fig. S2h), indicating that TRIM38 and USP29 independently interacts with and regulates cGAS."
32457395
sparser
"14,22,23 In our study, we found that a portion of USP29-cGAS associating spots were localized at perinuclear compartments after HSV-1 infection."
32457395