pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2

Haifeng Yang, Yoji Andrew Minamishima, Qin Yan, Susanne Schlisio, Benjamin L. Ebert, Xiaoping Zhang, Liang Zhang, William Y. Kim, Aria F. Olumi, William G. Kaelin

研究成果: Article

126 引用 (Scopus)

抜粋

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 a ubiquitin conjugating enzyme and a kinase. The latter activity, which promotes Card9 phosphorylation, links pVHL to control of NF-κB activity and tumorigenesis.

元の言語English
ページ(範囲)15-27
ページ数13
ジャーナルMolecular Cell
28
発行部数1
DOI
出版物ステータスPublished - 2007 10 12

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

フィンガープリント pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Yang, H., Minamishima, Y. A., Yan, Q., Schlisio, S., Ebert, B. L., Zhang, X., Zhang, L., Kim, W. Y., Olumi, A. F., & Kaelin, W. G. (2007). pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2. Molecular Cell, 28(1), 15-27. https://doi.org/10.1016/j.molcel.2007.09.010