Abstract 1037: Effects of stimulary GTP binding protein on the expression of histone deacetylase 6 and 8

Abstract

Abstract Stimulatory heterotrimeric GTP-binding protein (Gαs protein) is one of the four families of α subunit in G proteins, and stimulates cAMP production. Gαs protein is involved in many cellular signaling pathways, and regulates various cellular metabolism and gene expression. Histone deacetylases (HDACs) are the enzymes that perform epigenetic regulation of gene expression by removing of acetyl groups from histones. The HDAC family is composed of 18 proteins, and belongs to two major families: the zinc-dependent HDACs (class I, II, and IV), and NAD-dependent (sirtuins-like class III). Human class I HDACs include HDAC1, 2, 3 and 8, and human class II HDACs include HDAC4, 5, 6, 7, 9 and 10. Thus we analyzed the effect of Gαs on the expression of HDAC isoforms and its underlying molecular mechanism in H1299 human lung cancer cells. We found the expression of HDAC6 and HDAC8 isoforms were increased by the overexpression of the constitutively active Gαs proteins (GαsQL). The levels of HDAC6 and HDAC8 mRNA were increased following GαsQL expression. Treatment with forskolin also increased HDAC6 and HDAC8 levels, and treatment with H89 inhibited the increase in HDAC6 and HDAC8 levels induced by GαsQL. Furthermore, prostaglandin E2, a Gαs activating signal, also increased in HDAC8 levels. The increased expression of HDAC6 through this signaling pathway caused a decrease in acetylation level of α-tubulin. From these results, it is concluded that Gαs-cAMP signaling pathway augments HDAC6 and HDAC8 expression in H1299 lung cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1037. doi:10.1158/1538-7445.AM2011-1037