| 2010 |
MYCBP2 (E3 ubiquitin ligase) regulates internalization of TRPV1 in peripheral sensory neurons through inhibition of p38 MAPK signaling; loss of MYCBP2 constitutively activates p38 MAPK, which in turn inhibits TRPV1 internalization and prevents desensitization of capsaicin-induced calcium increases, prolonging thermal hyperalgesia. |
Conditional knockout mouse model (MYCBP2 deficiency in peripheral sensory neurons), p38 MAPK inhibition rescue experiments, calcium imaging, behavioral assays |
The Journal of biological chemistry |
High |
21098484
|
| 2010 |
Crystal structures of both PHR domains (MmPHR1 and MmPHR2) of mouse Mycbp2/Phr1 were determined, revealing a novel beta-sandwich fold composed of 11 antiparallel beta-strands. MmPHR1 has conserved loops on its apical surface; the structure explains the loss-of-function mutation Gly1092→Glu in the C. elegans ortholog RPM-1. |
X-ray crystallography (structural determination of PHR domains from Mus musculus Mycbp2) |
Journal of molecular biology |
High |
20156452
|
| 2013 |
Mycbp2 genetically interacts with Robo2 to regulate axon guidance in the mouse olfactory system; double heterozygous (Mycbp2+/−; Robo2+/−) mice show severe olfactory projection defects, and loss of Mycbp2 causes aberrant expression of Robo2 in dorsal olfactory sensory neurons. |
Genetic epistasis (double heterozygous mouse mutants), immunohistochemistry, analysis of olfactory sensory neuron projection topography |
Brain structure & function |
Medium |
23525682
|
| 2015 |
MYCBP2 functions as a guanosine exchange factor (GEF) for the small GTPase Ran in DRG neurons via its RCC1-like domain, facilitating GDP/GTP exchange of Ran in the nucleus. SUMOylated RanGAP1 physically interacts with MYCBP2 and inhibits its E3 ubiquitin ligase activity. Loss of MYCBP2 causes increased nuclear localization of Ran. |
Co-immunoprecipitation (SUMOylated RanGAP1–MYCBP2 interaction), subcellular fractionation and immunofluorescence (nuclear Ran localization in MYCBP2-deficient DRGs), GDP/GTP exchange assay |
The Journal of biological chemistry |
Medium |
26304119
|
| 2019 |
MYCBP2 forms an E3 ubiquitin ligase complex with FBXO45; this complex ubiquitylates and promotes proteasomal degradation of the tumor suppressor FBXW7 during prolonged mitotic arrest, thereby promoting mitotic slippage and preventing mitotic cell death. FBXO45 binds to a conserved acidic N-terminal motif of FBXW7 specifically during extended mitotic delay. |
Co-immunoprecipitation, ubiquitylation assays, proteasome inhibitor rescue, cell fate assays (mitotic slippage vs. cell death), MYCBP2 and FBXO45 knockdown/overexpression |
Cell death and differentiation |
High |
31285543
|
| 2024 |
MYCBP2 forms a complex with EPHB2 receptor tyrosine kinase facilitated by FBXO45; this complex does not require EPHB2 tyrosine kinase activity and is destabilized by ephrin-B ligand binding. Paradoxically, loss of MYCBP2 increases ubiquitination and decreases protein levels of EPHB2, indicating MYCBP2 stabilizes EPHB2. MYCBP2 is required for efficient EPHB2 signaling responses in cell lines and primary neurons. In C. elegans, the ephrin receptor VAB-1 shows genetic interactions with known MYCBP2 binding proteins. |
Proteomics screen, biochemical Co-IP, ubiquitination assays, MYCBP2 knockdown in cell lines and primary neurons, C. elegans genetic epistasis |
eLife |
High |
38289221
|
| 2023 |
MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor signaling; the MYCBP2-EPHB2 complex is facilitated by FBXO45, is independent of EPHB2 kinase activity, and is destabilized by ephrin-B ligands. Loss of MYCBP2 paradoxically increases EPHB2 ubiquitination and reduces its protein levels. |
Proteomics screen, Co-IP, ubiquitination assays, MYCBP2 knockdown, C. elegans genetics |
bioRxivpreprint |
Medium |
37693478
|
| 2022 |
RGS12 associates with MYCBP2 and activates it (enhances phosphorylation of MYCBP2) to promote ubiquitination and degradation of KIF2A in synovial fibroblasts, thereby promoting cilia elongation and number; this pathway drives inflammatory arthritis pathogenesis. |
LC-MS/MS, co-immunoprecipitation, overexpression/knockdown experiments, cilia imaging, in vivo RGS12-deficient mouse model |
Molecular therapy. Nucleic acids |
Medium |
36700049
|
| 2022 |
RGS12 associates with MYCBP2 in endothelial cells and enhances MYCBP2 phosphorylation to promote ciliogenesis and cilia elongation, driving angiogenesis in inflammatory arthritis. |
LC/MS and co-IP (RGS12-MYCBP2 interaction), overexpression/knockout experiments, cilia imaging |
Cell insight |
Medium |
37193553
|
| 2023 |
RGS12 associates with and activates MYCBP2 to ubiquitinate and degrade the cilia protein KIF2A in tumor-associated macrophages, thereby promoting M1 macrophage polarization and antitumor activity in oral squamous cell carcinoma. |
Co-IP, ubiquitination assays, RGS12 knockout macrophage model, MYCBP2 knockdown, in vitro and in vivo tumor models |
International journal of oral science |
Medium |
36797232
|
| 2024 |
MYCBP2 promotes ubiquitination and proteasomal degradation of S100A9 in microglia, promoting M2 phenotype polarization and reducing oxidative stress; MYCBP2 knockdown counteracts these beneficial effects in vitro and in vivo. |
Proteomic profiling (MYCBP2 enrichment in extracellular vesicles), MYCBP2 knockdown with functional rescue assays, ubiquitination assays, in vivo spinal cord injury model |
Advanced science |
Medium |
38896802
|
| 2025 |
MYCBP2 promotes ubiquitination and degradation of HNF4α via K33- and K48-linked polyubiquitin chains at lysines 300 and 307 of HNF4α, thereby modulating lipid metabolism gene expression in MASH-related hepatocellular carcinoma. |
In vitro ubiquitination assay, site-directed mutagenesis of HNF4α lysines, proteasome inhibitor treatment, co-IP, MYCBP2 knockdown/overexpression in cell lines and in vivo xenograft |
Oncogene |
High |
40181155
|
| 2025 |
MYCBP2 forms a novel E3 ligase complex with substrate specificity factor SPRYD3 (distinct from the FBXO45-MYCBP2 complex); SPRYD3-MYCBP2 promotes non-canonical ubiquitination on the deubiquitinase USP11 at cysteine 318, facilitating bipolar spindle formation and mitotic slippage during microtubule-targeting drug treatment. |
Co-IP (SPRYD3-MYCBP2 complex identification), ubiquitination assays, mutagenesis (USP11 C318), spindle assembly assays, cell fate assays |
The Journal of biological chemistry |
High |
41052634
|
| 2025 |
TRIB2 acts as a scaffold that binds UCP1 through its pseudokinase domain and recruits MYCBP2 as the E3 ligase to promote UCP1 ubiquitination and proteasomal degradation, linking thermogenic adaptation to post-translational UCP1 regulation. |
Co-IP (TRIB2-UCP1-MYCBP2 complex), ubiquitination assay, Trib2 knockout mouse model, functional thermogenesis assays |
bioRxivpreprint |
Medium |
|
| 2025 |
MYCBP2 targets KIF14 for ubiquitin-mediated proteasomal degradation in AML cells; MYCBP2 knockdown increases KIF14 protein stability and partially reverses cell cycle arrest and apoptosis effects caused by MYCBP2 depletion. |
siRNA knockdown, co-IP, ubiquitination assay, flow cytometry (cell cycle), in vivo xenograft |
The Journal of biological chemistry |
Medium |
42036047
|
| 2023 |
Loss-of-function variants in MYCBP2 cause a neurodevelopmental disorder (MDCD) with corpus callosum defects, developmental delay, and epilepsy. CRISPR-introduced disease-associated variants in C. elegans rpm-1 produce axonal abnormalities, altered habituation behavior, and abnormal autophagy marker (LGG-1/LC3) accumulation in variants affecting ubiquitin ligase activity, establishing loss of MYCBP2 ubiquitin ligase function as the pathogenic mechanism. |
CRISPR/Cas9 gene editing in C. elegans, in vivo axon imaging, behavioral assays, autophagy marker analysis, human patient variant identification by exome sequencing |
Brain : a journal of neurology |
High |
36200388
|
| 2002 |
Ikaros (IKZF1) binds regulatory regions of MYCBP2 and transcriptionally activates its expression in ALL cells; CK2 inhibition (which activates Ikaros) increases MYCBP2 expression in an IKZF1-dependent manner, placing MYCBP2 downstream of the Ikaros/CK2 axis. |
ChIP (Ikaros binding to MYCBP2 regulatory regions), CK2 inhibitor treatment, IKZF1 deletion correlation analysis, qRT-PCR and Western blot |
Oncotarget |
Medium |
26517351
|
| 2024 |
In a C. elegans model, introduction of the homologous HSAM-associated MYCBP2 missense variant results in reduced forgetting and increased membrane-bound glutamate receptor levels in relevant neurons, suggesting MYCBP2 normally promotes glutamate receptor removal/degradation to regulate memory. |
CRISPR knock-in of homologous variant in C. elegans, behavioral forgetting assays, glutamate receptor imaging |
bioRxivpreprint |
Low |
|