| 2007 |
TRIM41/RINCK was identified as an E3 ubiquitin ligase that interacts with protein kinase C (PKC) via the C1A domain of PKC (identified by yeast two-hybrid with PKCβ N-terminus as bait). TRIM41 ubiquitinates PKC both in vitro and in cells, leading to PKC degradation and reduced PKC levels; this mechanism is independent of phorbol ester-mediated PKC downregulation and applies to conventional, novel, and atypical PKC isozymes. |
Yeast two-hybrid screen, co-immunoprecipitation, in vitro and cellular ubiquitination assay, overexpression and siRNA knockdown with PKC level readout |
The Journal of biological chemistry |
High |
17893151
|
| 2005 |
TRIM41 protein (isoforms alpha and beta) localizes as speckles in both cytoplasm and nucleus of cells. Nuclear transport is mediated by an N-terminal segment common to both isoforms but is independent of a classical nuclear localization signal sequence, as determined by GFP fusion constructs and subcellular fractionation. |
GFP fusion live-cell imaging of truncation mutants, Western blot of cellular fractions |
Molecular biology reports |
Medium |
16022281
|
| 2018 |
TRIM41 interacts with influenza A virus nucleoprotein (NP) through its SPRY domain, ubiquitinates NP in vitro and in cells, and promotes NP polyubiquitination and proteasomal degradation, thereby restricting IAV infection. A TRIM41 RING-domain mutant lacking E3 ligase activity failed to inhibit IAV infection, demonstrating that E3 ligase activity is essential for antiviral function. |
Co-immunoprecipitation, in vitro ubiquitination assay, RNAi knockdown and CRISPR knockout of TRIM41, TRIM41 overexpression, E3 ligase-dead mutant analysis, viral infection assays |
Journal of virology |
High |
29899090
|
| 2018 |
TRIM41/RINCK binds to cGAS and promotes monoubiquitination of cGAS, positively regulating cGAS-mediated cGAMP synthesis and downstream type I interferon production. CRISPR/Cas9 deletion of RINCK dampened interferon production in response to cytosolic DNA and HSV-1 infection, and reduced TBK1 and IRF3 phosphorylation. |
CRISPR/Cas9 deletion, co-immunoprecipitation, ubiquitination assay, cGAMP measurement, TBK1/IRF3 phosphorylation assay, viral infection with IFN readout |
Cell & bioscience |
High |
29760876
|
| 2018 |
TRIM41 acts as an E3 ubiquitin ligase for the transcription factor ZSCAN21, promoting its degradation and thereby reducing SNCA (α-synuclein) transcription in neuronal cells. TRIM17 antagonizes this pathway by decreasing TRIM41-mediated degradation of ZSCAN21. TRIM41 knockdown increased SNCA expression, while ZSCAN21 silencing and TRIM17 silencing both reduced it. |
siRNA knockdown, co-immunoprecipitation, ubiquitination assay, gene expression analysis, patient variant functional assay |
Cell reports |
High |
30485814
|
| 2020 |
TRIM41 interacts with and ubiquitinates the nucleoprotein (N) of vesicular stomatitis virus (VSV), leading to proteasomal degradation of VSV-N and restriction of VSV infection. An E3 ligase-defective TRIM41 mutant failed to limit VSV infection, confirming that ubiquitin ligase activity is required. |
Co-immunoprecipitation, in vitro and cellular ubiquitination assay, TRIM41 overexpression and knockdown, E3 ligase-dead mutant, viral infection assay with proteasome inhibitor |
Viruses |
High |
31979016
|
| 2021 |
TRIM41 directly interacts with BCL10, a core component of the CBM (CARD-BCL10-MALT1) complex, and catalyzes K63-linked polyubiquitination of BCL10. This K63-ubiquitination of BCL10 recruits NEMO, leading to activation of NF-κB and the TBK1-IRF3 pathway downstream of nucleic acid sensing, and is required for innate antiviral cytokine and interferon production. |
Co-immunoprecipitation, ubiquitination assay (K63 linkage-specific), TRIM41 knockout mice (in vivo), macrophage nucleic acid transfection and viral infection assays, cytokine/IFN measurement, NF-κB/TBK1/IRF3 activation readouts |
Signal transduction and targeted therapy |
High |
33640899
|
| 2021 |
TRIM41 targets PKD1 for ubiquitin-mediated degradation; ANXA10 interacts with PKD1 and protects it from TRIM41-directed degradation. In melanoma cells, ANXA10-mediated stabilization of PKD1 suppresses SMAD6 expression (via TGF-β/SMAD pathway) to promote cell migration and metastasis. |
Co-immunoprecipitation, protein stability assay, ANXA10 knockout, ubiquitination assay (inferred), cell migration and in vivo metastasis assays |
Cancer letters |
Medium |
34324862
|
| 2022 |
TRIM41 is required for proper meiotic progression in male mice. Trim41 knockout spermatocytes exhibit overloading of SYCP3 on chromosome axes, particularly the X chromosome. A RING-domain deletion mutant of TRIM41 (which abolishes E3 ubiquitin ligase activity) phenocopies the full knockout, and mutant ΔRING-TRIM41 accumulates on chromosome axes with overloaded SYCP3, indicating TRIM41 regulates chromosome axis protein dynamics via its E3 ligase activity. |
Trim41 knockout mice, RING-domain deletion knock-in mutant mice, immunofluorescence of meiotic chromosome spreads for SYCP3, fertility assays |
PLoS genetics |
High |
35648791
|
| 2023 |
TRIM41 interacts with LINE-1 ORF2p and ubiquitinates it, promoting its proteasomal degradation and suppressing L1 retrotransposition. Nuclear cGAS enhances the association between ORF2p and TRIM41, thereby promoting TRIM41-mediated ORF2p degradation. Upon DNA damage, CHK2 phosphorylates cGAS at S120 and S305, which strengthens cGAS-TRIM41 association and further promotes ORF2p degradation. |
Co-immunoprecipitation, ubiquitination assay, TRIM41 knockdown, L1 retrotransposition reporter assay, phospho-mutant analysis, cancer-associated cGAS variant functional analysis |
Nature communications |
High |
38086852
|
| 2023 |
TRIM41/RINCK directly interacts with NRF2 and promotes its K48-linked polyubiquitination and proteasomal degradation in intestinal epithelial cells, suppressing NRF2 nuclear translocation and downstream antioxidant gene expression. IEC-specific Rinck knockout mitigated OTA/DSS-induced colitis and associated early colorectal cancer in mice. |
Co-immunoprecipitation, K48-linkage ubiquitination assay, IEC-specific Rinck knockout and overexpression transgenic mice, AAV-mediated knockdown, lentiviral knockdown, NRF2 nuclear localization assay, in vivo colitis and tumor models |
Phytomedicine |
High |
37844381
|
| 2023 |
circRNA_0067717 acts as a molecular scaffold that bridges TRIM41 and p53, promoting TRIM41-mediated ubiquitination and degradation of p53 in NPC paclitaxel-resistant cells. The 301–425 nt region of circRNA_0067717 binds TRIM41 and the 1–176 nt region binds p53. Blocking these regions reduced paclitaxel resistance. |
RNA pulldown, RNA immunoprecipitation, RNA FISH, siRNA knockdown, ubiquitination assay, deletion mapping of circRNA binding sites |
Cellular oncology |
Medium |
36705889
|
| 2024 |
TRIM41 promotes the ubiquitination and degradation of c-Maf in airway dendritic cells, reducing IL-10 expression and compromising tolerogenic DC properties, thereby contributing to airway allergy pathogenesis. |
Trim41 overexpression and inhibition in DCs, c-Maf protein level assay, IL-10 expression assay, murine airway allergy model |
iScience |
Medium |
38883815
|