Abstract 5746: TRAF1 is required for solar UV-induced skin carcinogenesis

Abstract

Abstract Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF protein family, which regulates the canonical and non-canonical NF-κB signaling cascades. Although aberrant TRAF1 expression in tumors is reported, the role of TRAF1 remains elusive. Here, we report that TRAF1 is required for skin carcinogenesis induced by chronic solar UV radiation. In vivo studies with solar UV exposure indicate that the deletion of TRAF1 results in the inhibition of AP-1 activity by down-regulating the induction of c-Fos and c-Jun by regulating ERK5 activity. Furthermore, we show that TRAF1 is required for solar UV-induced ERK5 activation. Mechanistic studies revealed that TRAF1 expression enhances the ubiquitination of ERK5 on K184, which is necessary for AP-1 activation. Altogether, our results suggest that TRAF1 mediates ERK5 activity by regulating the upstream effectors of ERK5 and also by modulating its ubiquitination status. Targeting TRAF1 function might lead to strategies for preventing and treating skin cancer. Citation Format: Hiroyuki Yamamoto, Joohyun Ryu, Eli Min, Naomi Oi, Ruihua Bai, Tatyana A. Zykova, Dong Hoon Yu, Margarita Malakhova, Kenji Moriyama, Ann M. Bode, Zigang Dong. TRAF1 is required for solar UV-induced skin carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5746. doi:10.1158/1538-7445.AM2017-5746