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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.
J Biol Chem. 2012 Jul 27; 287(31):25881-92.JB

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.

Authors+Show Affiliations

The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22685297

Citation

Peng, Cong, et al. "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." The Journal of Biological Chemistry, vol. 287, no. 31, 2012, pp. 25881-92.
Peng C, Zhu F, Wen W, et al. 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. J Biol Chem. 2012;287(31):25881-92.
Peng, C., Zhu, F., Wen, W., Yao, K., Li, S., Zykova, T., Liu, K., Li, X., Ma, W. Y., Bode, A. M., & Dong, Z. (2012). 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. The Journal of Biological Chemistry, 287(31), 25881-92. https://doi.org/10.1074/jbc.M112.359521
Peng C, et al. 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. J Biol Chem. 2012 Jul 27;287(31):25881-92. PubMed PMID: 22685297.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Peng,Cong, AU - Zhu,Feng, AU - Wen,Weihong, AU - Yao,Ke, AU - Li,Shengqing, AU - Zykova,Tatyana, AU - Liu,Kangdong, AU - Li,Xiang, AU - Ma,Wei-Ya, AU - Bode,Ann M, AU - Dong,Zigang, Y1 - 2012/06/08/ PY - 2012/6/12/entrez PY - 2012/6/12/pubmed PY - 2012/10/12/medline SP - 25881 EP - 92 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 287 IS - 31 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/22685297/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_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=22685297 DB - PRIME DP - Unbound Medicine ER -