4N0S

Complex of ERK2 with caffeic acid

4N0S の概要

• エントリーDOI: 10.2210/pdb4n0s/pdb
• 関連するPDBエントリー: 3SA0
• 分子名称: Mitogen-activated protein kinase 1, CAFFEIC ACID, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: caffeic acid complex, mitogen-activated protein kinase, signal-regulated kinase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle : P28482
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42479.86

構造登録者

Kurinov, I.,Malakhova, M. (登録日: 2013-10-02, 公開日: 2014-08-27, 最終更新日: 2024-10-30)

主引用文献

Yang, G.,Fu, Y.,Malakhova, M.,Kurinov, I.,Zhu, F.,Yao, K.,Li, H.,Chen, H.,Li, W.,Lim, D.Y.,Sheng, Y.,Bode, A.M.,Dong, Z.,Dong, Z.
Caffeic Acid Directly Targets ERK1/2 to Attenuate Solar UV-Induced Skin Carcinogenesis.
Cancer Prev Res (Phila), 7:1056-1066, 2014

PubMed Abstract: Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in coffee and reportedly has anticancer activities. However, the underlying molecular mechanisms and targeted proteins involved in the suppression of carcinogenesis by caffeic acid are not fully understood. In this study, we report that caffeic acid significantly inhibits colony formation of human skin cancer cells and EGF-induced neoplastic transformation of HaCaT cells dose-dependently. Caffeic acid topically applied to dorsal mouse skin significantly suppressed tumor incidence and volume in a solar UV (SUV)-induced skin carcinogenesis mouse model. A substantial reduction of phosphorylation in mitogen-activated protein kinase signaling was observed in mice treated with caffeic acid either before or after SUV exposure. Caffeic acid directly interacted with ERK1/2 and inhibited ERK1/2 activities in vitro. Importantly, we resolved the cocrystal structure of ERK2 complexed with caffeic acid. Caffeic acid interacted directly with ERK2 at amino acid residues Q105, D106, and M108. Moreover, A431 cells expressing knockdown of ERK2 lost sensitivity to caffeic acid in a skin cancer xenograft mouse model. Taken together, our results suggest that caffeic acid exerts chemopreventive activity against SUV-induced skin carcinogenesis by targeting ERK1 and 2.

PubMed: 25104643
DOI: 10.1158/1940-6207.CAPR-14-0141

実験手法

X-RAY DIFFRACTION (1.7992 Å)