Project description:JAB1 is a regulator of ubiquitin mediated protein degradation upstream of the 26S proteasome. JAB1 regulates the ubiquitin proteasome system through controlling the activity of the largest family of E3 ubiquitin ligases, the Cullin-RING Ligases. JAB1 is also a transcriptional co-factor contolling the expression of numerous genes and regulates musculoskeletal development in vivo. It is reported that JAB1 is overexpressed in many cancers, making it a potential oncogene. Thus, JAB1 has a highly spatiotemporal specific role in development and cancer pathogenesis. This study aims to determine the JAB1-mediated transcriptome that exists in osteosarcoma cells.
Project description:Fatty acid metabolism is critical for tumor progression, supplying bioenergetic and biosynthetic substrates to rapidly proliferating cancer cells. However, the precise mechanisms by which fatty acid metabolism influences breast cancer progression remain unclear. In this study, we aimed to explore the molecular mechanism by which JAB1 promotes breast cancer progression through regulating fatty acid metabolism. Our results shows that C-Jun activation domain-binding protein-1 (JAB1) is identified as an oncogene in breast cancer. JAB1 stabilizes CUL4B expression via deubiquitination, thereby promoting cell proliferation, invasion, and stemness. Mechanistically, JAB1 forms a transcriptional repressor complex with the Cullin 4B-Ring E3 ligase (CRL4B) complex, and co-occupy on the promoters of key fatty acid metabolism genes, PPARG and ACSL5, thus leading to their transcriptional repression. This disrupts fatty acid metabolism, increases mitochondrial oxygen consumption, and provide the energetic demands to breast cancer cells. Notably, JAB1 inhibition reverses chemotherapy resistance associated with CUL4B overexpression. These findings underscore the pivotal role of JAB1 in regulating breast cancer progression and indicate that JAB1 inhibitors could serve as promising therapeutics for patients with the elevated CUL4B expression.
Project description:The progression of acute myeloid leukemia (AML) is a complex process involving various cellular activities. In this context, our research focuses on the role of Jab1 as a key regulatory factor. Specifically, Jab1 plays a crucial role in regulating apoptosis and proliferation, providing support for the proliferation and survival of AML cells. As a c-JUN transcription co-activator, Jab1 participates in multiple transcriptional regulatory networks, influencing the gene expression of cells. Through RNA-seq data analysis, we present a detailed molecular framework, elucidating the impact of Jab1 downregulation on gene expression. This provides important insights for a comprehensive understanding of the molecular mechanisms underlying this disease, offering robust support for future research and therapeutic strategies.
