TRIM24 (Tripartite Motif Containing 24)

The patient with TRIM24::ALK fusion, following durable responses to alectinib and lorlatinib, relapsed with detection of on-target ALK kinase domain mutations (F1174V, I1171N) and MYC amplification on progression. Comprehensive molecular workup, including RNA-based NGS, is essential for detecting rare but actionable ALK rearrangements and optimizing therapeutic strategy. NGS of CSF was a valuable tool for the detection of clinically suspected leptomeningeal disease and disease monitoring.

ER-positive ZR75.1 breast cancer cells transduced with retroviral vectors were treated with endocrine (tamoxifen, fulvestrant) or CDK4/6i monotherapies (abemaciclib, palbociclib, ribociclib) or a combination of fulvestrant and ribociclib. Twenty of these loci were also identified as candidates for resistance to other CDK4/6i and to fulvestrant and ribociclib combination therapy, including TRPS1 and TRIM24-genes that are involved in resistance to endocrine therapy but have not yet been associated with resistance to CDK4/6i. The identification of unique and shared resistance-associated loci highlights the complexity of resistance pathways.

A PAH rat model was established by SU5416 (Su) injection combined with chronic hypoxia (Hx)...PF alleviated PAH and endothelial dysfunction by downregulating TRIM24 and preserving SIRT1 function. These findings reveal a novel mechanism by which PF protects against PAH via the TRIM24/SIRT1/NLRP3 axis.

Sex, follicular nodular disease, and Graves' disease were not significant predictors. Our findings suggest an association between fusion-driven thyroid neoplasia and florid CLT, warranting further investigation.

Further mechanistic insights revealed that NRBP1 phosphorylation at residue S42 was crucial for TRIM24-mediated ubiquitination, with residue K430 identified as the specific ubiquitination site targeted by TRIM24. Jointly, the above findings unveil a critical role for TRIM24 in GC tumorigenesis and metastatic progression, thereby positioning TRIM24 as a promising therapeutic target in GC management.

Among RB-RGs, SMARCA4, FBLL1, RRS1 and NVL were identified as prognostic genes for PCa, thereby providing a new direction for clinical disease treatment.

A general drug resistance to TRK-inhibition was documented. This study addresses the complex and adaptive nature of pediatric epithelioid glioblastomas and highlights the need for continued molecular profiling from relapses and various tumor regions to enable multitarget treatment approaches.

The resulting peptide-drug conjugates (PDCs) bind to TRIM24 with picomolar affinity and a slow dissociation rate (koff), which is driven by an in cis bivalent binding mode. Although the PDCs showed limited effects on breast cancer cell proliferation in vitro, this work underscores their potential as tools for studying previously unliganded reader domains and consequently advancing our understanding of multivalent epigenetic regulation in disease.

Furthermore, smoker patients have higher RFWD3 levels than non-smoker patients, and cigarette smoke extract, PM2.5, and benzo(a)pyrene upregulatesRFWD3 via transcription factor aryl hydrocarbon receptor. These results indicate a role of RFWD3 in tobacco smoke and haze (smohaze)-promoted immune evasion, inhibition of which activates STING-IFN signaling and synergizes with immune checkpoint inhibitors in NSCLC.

Moreover, chemical inhibition of AURKB suppresses tumor growth in subcutaneous mouse model and exhibits particular effectiveness against tumors derived from CRC cells characterized by prominent cytoplasmic TRIM24 distribution. Together, these findings reveal a critical role of TRIM24 in CRC cell proliferation, particularly through activating Wnt/β-catenin signaling.

Beyond enzymatic regulation, TRIM proteins exert non-canonical functions through epigenetic modulation and interactions with signaling networks. This review synthesizes current insights into the multifaceted roles of TRIM proteins in metabolic control and cell death, suggesting that ferroptosis may link TRIM proteins to lipid and amino acid metabolism, and highlights the connection between TRIM proteins and metabolic stress as a key area for future research.

Notably, pharmacological inhibition of TRIM24 using TRIM24-PROTAC (proteolysis-targeting chimera) effectively suppressed tumor growth in mice bearing SPOP-mutant prostate cancer cells. Collectively, these findings elucidate a pivotal role of SPOP mutations in modulating energy stress responses via TRIM24-mediated ULK1 ubiquitylation and underscore the therapeutic potential of targeting TRIM24 in SPOP-mutant prostate cancers.