TRIM37 (Tripartite Motif Containing 37)

Our findings establish the ALKBH5/IGF2BP1-TRIM37-RBMX signaling axis as a pivotal driver of PDAC progression, highlighting the intersection of m6A modification, ubiquitin signaling, and metabolic reprogramming. These findings may provide potential therapeutic avenues for this intractable malignancy.

Here, we found that IGF2BP3, acting as an m6A reader, promotes LUAD cell proliferation both in vivo and in vitro. Mechanistically, IGF2BP3 mediates the ubiquitination and degradation of p53 by reading the m6A-modified TRIM37 mRNA 3'UTR, thereby promoting tumorigenesis in LUAD. Importantly, shTRIM37 significantly inhibited IGF2BP3-driven tumor progression.

The results are in line with previous observations of segregation errors in human cell lines with TRIM37 defects. Further studies are required to elucidate the prevalence and implications of mosaic aneuploidies in Mulibrey nanism.

Biochemical assays revealed that IDR+ASH8 is primarily monomeric and binds TRIM37 via two separate coiled-coil motifs with mid-nanomolar affinity. We propose that the IDR+ASH8 motif is a bipartite degron for TRIM37, enabling it to target centrosome proteins and adjust their levels.

This dynamic regulation arises because TRIM37 preferentially associates with the activated form of Tip60. Collectively, our findings identify the TRIM37-Tip60 axis as a critical regulator of host DDR in response to P. aeruginosa infection, offering new insights into infection-associated DDR and therapeutic strategies.

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.