TRIP12 (Thyroid Hormone Receptor Interactor 12)

Finally, we found that the formation of TRIP12-mediated condensates alters cell cycle progression, genome accessibility, and transcription. Altogether, this study reveals a novel dynamic role for TRIP12 in chromatin compaction independently of its ubiquitin ligase activity with important consequences on nuclear processes.

Serine 440 (S440), located outside the kinase domain (representing over 55% of CIT-associated phospho-signalling events across 100 experimental conditions, including Enterovirus A71 infection, metformin, and interleukin-33), was identified as its predominant phosphosite...Aberrant phosphorylation of CIT_S440 observed across cancers of the breast, colon, and bladder suggests CIT_S440 as a potential onco-phosphosite critically involved in cellular checkpoint signalling. These findings suggest that CIT_S440 functions as a promising therapeutic target, and the phosphosite-centric regulatory network derived in this study could serve as a platform to evaluate its phosphosite-specific therapeutic interventions.

Collectively, our study identifies a feedback regulatory loop between SOX12 and RNF168 that promotes DNA damage repair and cisplatin resistance in esophageal cancer cells.

The Trip12-mediated reduction of Fzd9b surface expression dampens Wnt9a/Fzd9b signaling, affecting HSC proliferation in zebrafish. Our findings reveal a receptor-specific regulatory mechanism, with implications for targeted Wnt pathway therapies.

To our knowledge, this represents the first comprehensive proteomics framework of the HPV16 E6 interactome under small-molecule treatment conditions. These findings support a model in which AA facilitates proteasome-mediated elimination of E6, and the dataset itself provides a timely and valuable resource for HPV biology and therapeutic development.

The caspase-1 specific inhibitor, VX-765, partially abolished the anti-viability, and pro-pyroptosis effects of oe-USP7, indicating USP7 overexpression prevented the malignant phenotype of ccRCC cells by enhancing caspase-1 dependent pyroptosis...The similar effects of oe-USP7 on ccRCC development were found in ccRCC mice. USP7 mediated TRIP12 deubiquitination inhibited ccRCC progression by enhancing pyroptosis.

In this manner, TRIP12 accelerates stress response silencing as oxidative stress is being resolved but limits NRF2 activation during stress. The need for dynamic control of NRF2 degradation therefore comes at the cost of diminished stress signaling, suggesting that TRIP12 inhibition could be used to treat degenerative pathologies characterized by ROS accumulation.

Our findings support a model in which TRIP12 ubiquitylates BRG1 in the presence of Wnt and promotes its interaction with β-catenin in the nucleus, in order to recruit SWI/SNF to Wnt target genes. Our studies suggest a general mechanism by which cell signaling induces the interaction between BRG1 and pathway-specific transcription factors to recruit SWI/SNF complexes to their appropriate target genes.

WDR11-DT-induced dual restraints of PARP1 and the HR pathway lead to the accumulation of double-strand breaks as well as synthetic lethal effects of malignant cells, which, thereby, enhances radiosensitivity and inhibits progression of lung cancer. These results extend our current knowledge of radio-biology and elucidate that WDR11-DT may be a new target for boosting cancer radiotherapy.

We elucidated the molecular mechanisms underlying the simultaneous occurrence of ferroptosis resistance and immune suppression in PDAC patients. Our study provides a novel therapeutic strategy that could promote ferroptosis in tumour cells and increase immunotherapy efficacy.

Our study has identified two novel pathways that play a role in p53-mediated growth restriction. Moreover, we have highlighted the interaction between the Hippo and the p53 pathways. Interestingly, we have shown that TRIP12 plays an important function in the p53 pathway by selectively affecting its role as a transcription factor.

Immunohistochemistry analysis further reveals a link between DOPEY1, USP7, and TRIP12 expression, H. pylori infection, and GC progression. These findings demonstrate that H. pylori-induced upregulation of DOPEY1 drives p53 degradation via the USP7/TRIP12 axis, contributing to gastric tumorigenesis, and highlight DOPEY1 as a potential therapeutic target for H. pylori-associated GC.