PSMB10 (Proteasome 20S Subunit Beta 10)

Collectively, the TZM-blB8-mCherryB10-CFP cell line provides a tool to interrogate immunoproteasome functions independently of intermediate proteasomes, whereas SW620B8-mCherryB5-GFP cells enable visual discrimination between constitutive and β5i-containing proteasomes both in vitro and in vivo. Generated cell lines provide a novel platform for dissecting proteasome functions, addressing the distinct properties of individual proteasome forms, and assessing the impact of diverse compounds on the proteasome repertoire in cultured cells and in tumor xenografts.

Carfilzomib synergized with BCL2 family protein inhibitors (navitoclax or AZD5991), suggesting that drug combinations could be used to reduce the dose of each drug to minimize toxicity. Notably, thymic carcinomas differed from squamous cell carcinomas in other organs by higher levels of β5i (PSMB8) and constitutive proteasome β5 (PSMB5). We hypothesize that TC (and probably many TH) are uniquely suited for treatment with proteasome inhibitors alone or in combination with selective BH3 mimetics.

Our real-life cohort analysis confirms the limitations of standalone biomarkers like PD-L1. We identified gene expression-based markers with strong prognostic and predictive value for ICI treatment outcomes.

The prognostic model built on 7 macrophage-linked genes exhibited robust prediction performance in BLCA. The M2 macrophage phenotype was notably enriched in the high-risk cohort and appeared to cause elevated tumor invasiveness. Immune infiltration analysis suggested that the high-risk population showed a weaker response to immune checkpoint inhibitor (ICI) treatment. Among all identified genes, DEDD2 may serve as a promising prognostic biomarker for BLCA.

The findings underscore the adaptability of the ubiquitin-proteasome system in maintaining cellular proteostasis by compensatory mechanisms that counteract the lack of Lmp2. The Psmb9KO line can serve as a valuable model for examining the function of immunoproteasomes in proteostasis regulation during early mammalian embryogenesis differentiation.

The risk score model provides a new perspective for screening potential populations to benefit from immunotherapy and predicting their survival. FUCA1 may be a potential prognostic biomarker and promising therapeutic target for patients with MPM.

PSMB10 is a key candidate molecular target for eradicating drug-resistant LSCs via senescence and immune regulation.

P=N/A, N=300, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Immunoproteasome subunits, in particular PSMB9, are immune microenvironment-related molecules of MIBC and are promising signatures for survival prediction in response to immunotherapy of MIBC.

A different IL-1 pathway gene expression was observed in the synovial tissues of early treatment-naïve RA/T2D patients, linked to decreased expression of the ubiquitin-proteasome system. These findings may provide a mechanistic explanation of the observed clinical benefits of IL-1 inhibition in patients with RA and concomitant T2D.

In terms of immune-oncology-related gene expression, discordant p16+/HPV- OPCs are much more closely aligned with p16-/HPV-OPCs and quite distinct from p16+/HPV+ tumours. This is consistent with previously described prognostic patterns (p16+/HPV+ >> p16+/HPV- > p16-/HPV-) and underlines the need for dual p16 and HPV testing to guide clinical decision making.

This cell line can be utilized for the research on subcellular localization, dynamic expression, and activity of PSMB9 in live cells at different infection conditions and disease stages. It also provides a model for the stable cell lines construction of other immunoproteasome subunits PSMB8 and PSMB10.