97 research outputs found
pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2
The VHL tumor suppressor protein (pVHL) is part of an E3 ubiquitin ligase that targets HIF for destruction. pVHL-defective renal carcinoma cells exhibit increased NF-κB activity but the mechanism is unclear. NF-κB affects tumorigenesis and therapeutic resistance in some settings. We found that pVHL associates with the NF-κB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C-terminus by CK2. Elimination of these sites markedly enhanced Card9's ability to activate NF-κB in VHL+/+ cells and Card9 siRNA normalized NF-κB activity in VHL−/− cells and restored their sensitivity to cytokine-induced apoptosis. Furthermore, downregulation of Card9 in VHL−/− cancer cells reduced their tumorigenic potential. Therefore pVHL can serve as an adaptor for both an ubiquitin conjugating enzyme and for a kinase. The latter activity, which promotes Card9 phosphorylation, links pVHL to control of NF-κB activity and tumorigenesis
Stem cell biology is population biology: differentiation of hematopoietic multipotent progenitors to common lymphoid and myeloid progenitors
Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model
New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment
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