Tumor Necrosis Factor Receptor-associated Factor Family Protein 2 Is a Key Mediator of the Epidermal Growth Factor-induced Ribosomal S6 Kinase 2/cAMP-responsive Element-binding Protein/Fos Protein Signaling Pathway

作者：Peng Cong; Zhu Feng; Wen Weihong; Yao Ke; Li Shengqing; Zykova Tatyana; Liu Kangdong; Li Xiang; Ma Wei Ya; Bode Ann M; Dong Zigang^*

来源：Journal of Biological Chemistry, 2012, 287(31): 25881-25892.

DOI：10.1074/jbc.M112.359521

TRAF2 has an important function in mediating the TNF-R signaling pathway toward activation of NF-kappa B and JNKs. Here we reveal a novel function of TRAF2 in the epidermal growth factor (EGF) signaling pathway. Knockdown of TRAF2 blocked EGF-induced AP-1 activity and anchorage-independent cell transformation. Notably, we showed that EGF induces ribosomal S6 kinase 2 (RSK2) ubiquitination, and knocking down TRAF2 suppresses ubiquitination of RSK2 induced by EGF. We also found that TRAF2 affects RSK2 activity through RSK2 ubiquitination. RSK2 plays a critical role in AP-1 activity mediated through CREB and c-Fos, which regulates anchorage-independent cell transformation. In addition, TRAF2 is overexpressed in colon cancer and required for colon cancer development, suggesting that TRAF2 might be a potential molecular target for cancer prevention and treatment.

• 出版日期2012-7-27