N4BP1 (NEDD4 Binding Protein 1)

N4BP1 not only drives cancer cell evolution but also establishes an immune-suppressive microenvironment. N4BP1 is an endoribonuclease that specifically regulates a subset of mRNA targets (including CCL2 and GM-CSF) and plays an essential role in oral cancer.

Eliminating FADD, the adaptor protein that promotes caspase-8 oligomerization, prevented this perinatal lethality. Collectively, our results suggest that cFLIP forms heterodimers with caspase-8 D387A to promote apoptosis in some contexts, while limiting the activity of caspase-8 D387A homodimers in others.

Cell-cell communication analysis revealed that SOCS3+ exhausted T cells interact with myeloid cells through the MIF signaling pathway. Integrated single-cell transcriptomic analysis demonstrates that SOCS3+ exhausted T cells promote tumor resistance to cytotoxic killing and serve as a robust prognostic biomarker in ccRCC patients.

This alters PTEN's subcellular localization, promoting nuclear PTEN and reducing cytoplasmic PTEN, which in turn leads to increased RAD51 for DNA repair and activation of the PI3K-AKT-mTOR pathway for cell proliferation, contributing to doxorubicin resistance. Our study reveals a novel mechanism of doxorubicin resistance mediated by exosomal miR-92b-5p and provides potential therapeutic targets for overcoming drug resistance in AML.

Additionally, we measured levels of HBV pregenomic RNA (pgRNA) and covalently closed circular DNA in the RBP-transfected cells and confirmed that N4BP1 binds pgRNA directly and regulates both the 3.5 and 2.4/2.1 kb HBV RNA. In summary, N4BP1 is a newly identified host factor able to counteract HBV production by regulating 3.5 and 2.1/2.4 kb HBV RNA.

We also show that mouse N4bp1 resists human enteroviral 3Cpro cleavage. In contrast, rodent enteroviral EMCV 3Cpro can target human and mouse N4BP1 for cleavage at different residues, which indicates that future investigations are needed to elucidate the potential mechanisms involved.

Here, we will summarize what is known about the fate and functions of individual MALT1 substrates and how their cleavage contributes to the biological functions of the MALT1 protease. We will outline what is needed to better connect critical pathophysiological roles of the MALT1 protease with the cleavage of distinct substrates.

Under proapoptotic conditions, caspase-8 mediates proteolytic processing of N4BP1, resulting in rapid degradation of N4BP1 by the 26 S proteasome, and acceleration of apoptosis. In summary, our findings demonstrate that N4BP1 dimerization creates a novel type of ubiquitin reader that selectively recognises linear ubiquitin which enables the timely and coordinated regulation of TNFR1-mediated inflammation and cell death.

This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.

We also demonstrated more comprehensive key pathways affected by HBV integration and elucidated the mechanism for inversion and frequent translocation events due to virus integration. Apart from the great significance of the rule of HBV integration, the current study also provides valuable insights into the mechanism of virus integration.