RSK2 plays a key role in proliferation and cell transformation by regulating downstream targets that include transcription factors and protein kinases. Kaempferol, a natural compound that is abundant in many foods such as green onion (∼800 mg/kg), was identified as an RSK2 inhibitor. The authors provide evidence showing that kaempferol inhibits the N-terminal, but not C-terminal, kinase activity of RSK2 by interacting with Val82 and Lys100, which are critical amino acids for RSK2 activity. Computational modeling showed that kaempferol occupies the active pocket by direct binding with the backbone of Asp148 and Leu150 and forming a hydrogen bond with Lys100 and a hydrophobic interaction with Val82 and Leu147. The cover shows the interacting amino acids of the RSK2 N-terminal kinase domain and kaempferol. For details, see the article by Cho and colleagues on page 4398 of this issue.

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