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

Cong Peng, Feng Zhu, Weihong Wen, Ke Yao, Shengqing Li, Tatiana Zykova, Kangdong Liu, Xiang Li, Wei-Ya Ma, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

TRAF2 has an important function in mediating the TNF-R signaling pathway toward activation of NF-κB 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.

Original languageEnglish (US)
Pages (from-to)25881-25892
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number31
DOIs
StatePublished - Jul 27 2012

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