TRIM37 (Tripartite Motif Containing 37)

Structural analysis of multiple X-ray cocrystal structures enabled the design of analogs that demonstrated excellent kinome selectivity. Tumor regression was observed in efficacy studies of compound 25 in a CHP-134 neuroblastoma xenograft tumor model.

TRIM37 expression is associated with increased cell proliferation, regardless of subtype; however, it is strongly associated with reduced immune activity, worse response to chemotherapy, and poor prognosis in ER-positive/HER2-negative BC, whereas it was associated with better response to chemotherapy and no relationship with survival in TNBC. Our results provide critical insights into the clinical application of TRIM37-targeted therapies.

In an experimental autoimmune encephalomyelitis (EAE) model, overexpression TRIM37 significantly suppressed neuroinflammation mediated by microglia, reduced the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and alleviated demyelination lesions (as evidenced by reduced myelin damage shown by Luxol fast blue (LFB) staining, P < 0.001), while simultaneously increasing MBP expression levels (P < 0.001). In conclusion, targeting the TRIM37-PEX5 axis holds promise as a novel strategy for improving myelin damage and providing neuroprotection in MS, offering a theoretical basis for interventions in metabolism-oxidative stress-related diseases.

These results validated the significant roles of O-GlcNAcylation of UBAP2L in ccRCC sunitinib resistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of ccRCC.

SPTBN1 overexpression suppressed apoptosis, oxidative stress, and inflammation in ox-LDL-treated HUVECs by regulating the TRIM37/TRAF2/NF-κB pathway, thereby inhibiting AS development in mice. Our findings advance understanding of the molecular basis of endothelial homeostasis and identify a potential therapeutic target for AS.

Further evaluation in MCF-7 cells revealed its ability to suppress clonogenic survival, induce mitotic arrest, and trigger apoptosis. These findings highlight 5f as a promising PLK4 inhibitor warranting further investigation.

RP-1664 showed robust anti-tumor activity in 14/15 neuroblastoma xenograft models and significantly extended survival in a transgenic murine neuroblastoma model. These data support biomarker-directed clinical development of PLK4 inhibitors for high-risk neuroblastoma and other cancers with somatically acquired TRIM37 overexpression.

This review identifies TRIM proteins that are involved in urological cancers. Some of these proteins have the potential to be the therapeutic target.

In the pharmacokinetic study, compound K22 exhibited a good area under the curve (AUC0-t = 447 ± 47.6 ng h mL-1) and acceptable half-life (T 1/2 = 1.07 ± 0.111 h). In summary, compound K22 has further research value as a PLK4 inhibitor.

Oligomerization resulting from RING-RING interactions and conformational regulation through B-box 2-B-box 2 interfaces are essential for TRIM37 to suppress centrobin condensate formation. These results indicate that, similar to antiviral TRIM ligases, TRIM37 activation is coupled to detection of oligomerized substrates, facilitated by recognition of specific motifs in the substrate, to enforce ubiquitination-mediated clearance of ectopic centrosomal protein assemblies.

Using optogenetics, we demonstrate that the E3 activity of TRIM37 is directly coupled to the assembly state of its substrates, being activated only when centrosomal proteins cluster into higher-order assemblies resembling MTOCs. This regulatory framework provides a mechanistic basis for understanding TRIM37-driven pathologies and echoes the restriction of the human immunodeficiency virus capsid by TRIM5, thus unveiling a conserved activation blueprint among TRIM proteins to control turnover of complexes assembled at the mesoscale level.