Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By comparing protein profiles of nasopharyngeal carcinoma HONE1 cells to transformed nasopharyngeal epithelial NP 69 cells, several clusters of differentially expressed proteins were identified. The increased expression of cytokeratin 8 (CK8) and pyruvate kinase M2 was a common feature in four NPC cell lines compared to the two transformed epithelial cell lines. Suppression of CK8 was associated with the sensitivity to cisplatin in HONE1 cells; while overexpression of CK8 provided resistance to cisplatin-mediated apoptosis; and this protection occurred through an enhanced phosphorylation of c-Jun NH(2)-terminal kinase (JNK). Our findings implicate an underlying molecular mechanism in which CK8 is required for cisplatin resistance.
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PMID:Cytokeratin 8 silencing in human nasopharyngeal carcinoma cells leads to cisplatin sensitization. 1835 40

Neural stem and progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes and oligodendrocytes. However, the mechanisms underlying the decision of a stem cell to either self-renew or differentiate are incompletely understood. We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation. The absence of Fbw7 in the mouse brain caused severely impaired stem cell differentiation and increased progenitor cell death. Fbw7 deficiency resulted in accumulation of two SCF(Fbw7) substrates, the transcription factors active Notch1 and N-terminally phosphorylated c-Jun. Genetic and pharmacological rescue experiments identified c-Jun as a key substrate of Fbw7 in controlling progenitor cell viability, whereas inhibition of Notch signaling alleviated the block in stem cell differentiation. Thus Fbw7 controls neurogenesis by antagonizing Notch and c-Jun N-terminal kinase (JNK)/c-Jun signaling.
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PMID:Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. 2097 53