Computational and biochemical discovery of RSK2 as a novel target for epigallocatechin gallate (EGCG)

Hanyong Chen, Ke Yao, Xiaoyu Chang, Jung Hyun Shim, Hong Gyum Kim, Margarita Malakhova, Dong Joon Kim, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). Protein interaction with EGCG is a critical step for mediating the effects of EGCG on the regulation of various key molecules involved in signal transduction. By using computational docking screening methods for protein identification, we identified a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2), as a novel molecular target of EGCG. RSK2 includes two kinase catalytic domains in the N-terminal (NTD) and the C-terminal (CTD) and RSK2 full activation requires phosphorylation of both terminals. The computer prediction was confirmed by an in vitro kinase assay in which EGCG inhibited RSK2 activity in a dose-dependent manner. Pull-down assay results showed that EGCG could bind with RSK2 at both kinase catalytic domains in vitro and ex vivo. Furthermore, results of an ATP competition assay and a computer-docking model showed that EGCG binds with RSK2 in an ATP-dependent manner. In RSK2+/+ and RSK2-/- murine embryonic fibroblasts, EGCG decreased viability only in the presence of RSK2. EGCG also suppressed epidermal growth factor-induced neoplastic cell transformation by inhibiting phosphorylation of histone H3 at Ser10. Overall, these results indicate that RSK2 is a novel molecular target of EGCG.

Original languageEnglish (US)
Article numbere0130049
JournalPloS one
Issue number6
StatePublished - Jun 17 2015

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© 2015 Chen et al.


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