Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rheumatoid arthritis is a chronic, inflammatory joint disease leading to inflammation of synovial membrane that lines the joints. This inflammation further progresses and results in destruction of joints and surrounding cartilages. The underlying factors can be oxidative stress, pro-inflammatory mediators, imbalance and attenuation between various enzymes and proteins (like nuclear factor erythroid 2 related factor 2/Nrf2 and ubiquitin). Protein degradation pathways comprises of lysosomal, proteasomal pathway, and autophagosome (that are carried out in mammalian cells) are regulated through ubiquitin. Ubiquitin proteasomal system is dominating pathway for carrying out non-lysosomal proteolysis of intracellularly proteins. Fundamental processes including cell cycle progression, process of division, apoptosis, modulation of immune responses and cell trafficking are regulated by process of ubiquitination. Ubiquitin proteasomal pathway (UPP) includes ubiquitin moieties which are covalently attached to proteins and guides them proteasome for degradation. Misfolded, oxidized and damaged proteins which are responsible for critical processes, are major targets of degradation process. Any alteration in this system leads to dysregulated cellular homeostasis; progressively leading to numerous diseases including rheumatoid arthritis. Factors including TAK1, TRAF6 undergo are required for the progression of disease and thus contributes towards pathology of inflammatory disorders such as rheumatoid arthritis. This review will include all linked aspects which contribute its major role in rheumatoid arthritis.
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PMID:Ubiquitination in rheumatoid arthritis. 3296 Dec 30

The key component in the UFM1 conjugation system, UFM1-binding and PCI domain-containing protein 1 (UFBP1), regulates many biological processes. Recently it has been shown that low UFBP1 protein level is associated with the worse outcome of gastric cancer patients. However, how it responses to the sensitivity of gastric cancer to chemotherapy drugs and the underlying molecular mechanism remain elusive. Here, we discovered that high UFBP1 expression increases the progression-free survival of advanced gastric cancer patients treated with platinum-based chemotherapy. Cell-line based studies unveiled that UFBP1 expression enhances while UFBP1 knockdown attenuates the sensitivity of gastric cancer cells to cisplatin. High-throughput SILAC-based quantitative proteomic analysis revealed that the protein level of aldo-keto reductase 1Cs (AKR1Cs) is significantly downregulated by UFBP1. Flow cytometry analysis showed that UFBP1 expression increases while UFBP1 knockdown reduces reactive oxygen species upon cisplatin treatment. We further disclosed that UFBP1 attenuates the gene expression of AKR1Cs and the transcription activity of the master oxidative stress-response transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2). Detailed mechanistic studies manifested that UFBP1 promotes the formation of K48-linked polyubiquitin chains on Nrf2 and thus augments its proteasome-mediated degradation. Experiments using genetic depletion and pharmacological activation in vitro and in vivo demonstrated that UFBP1 enhances the sensitivity of gastric cancer cells to cisplatin through the Nrf2/AKR1C axis. Overall, this work discovered a novel prognostic biomarker for gastric cancer patients treated with platinum-based chemotherapy and elucidated the underlying molecular mechanism, which may benefit to future personalized chemotherapy.
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PMID:UFBP1, a key component in ufmylation, enhances drug sensitivity by promoting proteasomal degradation of oxidative stress-response transcription factor Nrf2. 3321 17


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