Abstract 3011: Correlation of PERK activation with increased GRP78-binding in UVB-irradiated HaCaT cells

Abstract

Abstract Ultraviolet (UV) light has been shown to be a potential human carcinogen, and it is widely accepted that UV exposure can impact protein expression via both transcriptional and translational regulation. PERK is one of the eIF2α kinases that is activated and inhibits protein synthesis upon UV irradiation. However, the mechanism for UV-induced PERK activation is not fully elucidated. In this study, we evaluated the role of GRP78/BiP, an inhibitory PERK-binding protein, in the regulation of PERK activity in UVB irradiated cells. Our data showed that while PERK expression was reduced in both human keratinocytes (HaCaT) and mouse embryonic fibroblasts (MEF) cells, GRP78/BiP expression remained steady in HaCaT and slightly increased in MEF cells after UVB irradiation. Our data also showed that the Tyr phosphorylation of PERK, an indication of activation, was increased after UVB irradiation, which confirmed the role of PERK in UV-induced translational regulation. Unexpectedly, a co-immunoprecipitation analysis indicated PERK activation was accompanied with an increase in PERK-bound GRP78/BiP in the irradiated HaCaT cells. Based on these results, we propose that UV-induced PERK activation might be GRP78/BiP-independent, and its activation pathway in HaCaT cells may be unique from other cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3011. doi:1538-7445.AM2012-3011