| 2003 |
T3JAM (TRAF3IP3) was identified as a novel protein that specifically associates with TRAF3 but not other TRAF family members. Co-expression of T3JAM with TRAF3 recruits TRAF3 to the detergent-insoluble fraction, and T3JAM and TRAF3 synergistically activate JNK but not NF-κB, indicating T3JAM functions as an adapter molecule specifically regulating TRAF3-mediated JNK activation. |
Co-immunoprecipitation, subcellular fractionation, overexpression reporter assays for JNK and NF-κB activation |
FEBS letters |
Medium |
14572659
|
| 2015 |
TRAF3IP3 localizes to the Golgi and is required for TCR-stimulated ERK and MEK activation during thymocyte positive selection. Mechanistically, TRAF3IP3 recruits MEK to the Golgi, facilitating the interaction of MEK with its activator BRAF. Transgenic expression of constitutively active MEK rescues the T cell development block in Traf3ip3 knockout mice. |
Conditional knockout mice, T cell development assays, subcellular fractionation/localization, co-immunoprecipitation, genetic rescue with constitutively active MEK |
The Journal of experimental medicine |
High |
26195727
|
| 2015 |
TRAF3IP3 promotes autophagy via an ATG16L1-binding motif. Loss of TRAF3IP3 in knockout mice leads to diminished autophagy and increased apoptosis in marginal zone B cells, impairing their survival and resulting in defective T-independent type II immune responses. |
Knockout mice, autophagy assays, apoptosis assays, mutational analysis of ATG16L1-binding motif |
Clinical and experimental immunology |
Medium |
26011558
|
| 2018 |
Lysosomal TRAF3IP3 restricts mTORC1 signaling in regulatory T cells by recruiting the serine-threonine phosphatase catalytic subunit PP2Ac to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Loss of TRAF3IP3 causes hyper-glycolytic metabolism via excessive mTORC1 activity, destabilizing Treg cells. |
T reg-specific conditional knockout mice, co-immunoprecipitation of PP2Ac-Raptor interaction, lysosomal fractionation/localization, metabolic assays, mTORC1 activity measurements |
The Journal of experimental medicine |
High |
30115741
|
| 2019 |
TRAF3IP3 accumulates on mitochondria upon virus infection and mediates the recruitment of TRAF3 to MAVS, thereby facilitating TBK1-IRF3 activation for interferon production. Traf3ip3-deficient mice show severely compromised interferon production and increased susceptibility to RNA virus infection. |
Knockout mice, virus infection assays, co-immunoprecipitation, mitochondrial localization assays, interferon production measurements |
The EMBO journal |
High |
31390091
|
| 2019 |
TRAF3IP3 at the trans-Golgi network recruits MEK1 and facilitates ERK phosphorylation and nuclear translocation in NKT2 cells, promoting their functional maturation. T-cell-specific deletion of TRAF3IP3 reduces thymic NKT2 cells and impairs IL-4 production. |
T-cell-specific conditional knockout mice, trans-Golgi network localization assays, co-immunoprecipitation of MEK1, ERK phosphorylation and nuclear translocation assays |
Cellular & molecular immunology |
Medium |
31076725
|
| 2020 |
TRAF3IP3 suppresses cytosolic RNA-triggered IFN-I production by interacting with endogenous TRAF3 and TBK1, leading to K48-linked (degradative) ubiquitination of TBK1 at its K372 residue in a DTX4-dependent fashion. Myeloid-specific deletion of Traf3ip3 increases RNA virus-triggered IFN-I production and reduces susceptibility to virus. |
Myeloid-specific conditional knockout mice, overexpression systems, co-immunoprecipitation of TRAF3 and TBK1, ubiquitination site mapping (K372), DTX4-dependence established by genetic manipulation, virus susceptibility assays |
Nature communications |
High |
32366851
|
| 2022 |
TRAF3IP3 is cleaved by EV71 3C protease at the 87Q-88G site, which partially resists TRAF3IP3-mediated inhibition of EV71 replication. TRAF3IP3 possesses nuclear localization signal (NLS) and nuclear export signal (NES); the NES contributes to TRAF3IP3-mediated alteration of 3Cpro localization and inhibition of EV71 replication. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, cleavage site mapping, NLS/NES functional analysis, viral replication assays in Jurkat and RD cells |
Frontiers in microbiology |
Medium |
35814660
|
| 2024 |
TRAF3IP3 blocks mitophagy to exacerbate myocardial ischemia-reperfusion injury by promoting the degradation of NEDD4 protein. Knockdown of TRAF3IP3 induces mitophagy and enhances mitochondrial function, alleviating myocardial injury in I/R rats. |
Co-immunoprecipitation, CHX (cycloheximide chase) assays, immunoblot, immunostaining, knockdown in H9C2 cells, in vivo I/R rat model |
Cardiovascular toxicology |
Medium |
39240426
|
| 2025 |
TRAF3IP3 triggers ER stress via the PERK/ATF4/CHOP pathway in lung adenocarcinoma cells and facilitates recruitment of STRN3 to the ER lumen through its transmembrane domain. TRAF3IP3-induced ER stress-mediated apoptosis and cytoprotective autophagy are dependent on STRN3, identified by IP-MS as a direct downstream interactor. |
IP-MS identification of STRN3 as binding partner, co-immunoprecipitation, transmembrane domain mutational analysis, ER stress pathway analysis (PERK/ATF4/CHOP), STRN3 knockdown rescue experiments, cell viability/apoptosis assays |
Advanced science |
Medium |
40068093
|