An IFN-γ–stimulated ATF6–C/EBP-β–signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy

• DOI: 10.1073/pnas.1119273109
• Publication Date: 2012-06-14T04:59:10Z
• Authors: Padmaja Gade; Girish Ramachandran; Uday B. Maachani; Mark A. Rizzo; Tetsuya Okada; Ron Prywes; Alan S. Cross; Kazutoshi Mori; Dhananjaya V. Kal...
• Keywords: ATF6; Activating transcription factor

The IFN family of cytokines operates a frontline defense against pathogens and neoplastic cells in vivo by controlling the expression several genes. death-associated protein kinase 1 (DAPK1), an IFN-γ–induced enzyme, controls cell cycle, apoptosis, autophagy, tumor metastasis, its is frequently down-regulated number human tumors. Although biochemical action DAPK1 well understood, mechanisms that regulate are unclear. Previously, we have shown transcription factor C/EBP-β required for basal . Here, show ATF6, ER stress-induced factor, interacts with IFN-stimulated manner obligatory Dapk1 expression. proteolytic processing ATF6 ERK1/2-mediated phosphorylation necessary these interactions. More importantly, IFN-γ failed to activate autophagic response lacking either or C/EBP-β. Consistent observations, Atf6 −/− mice were highly susceptible lethal bacterial infections compared wild-type mice. These studies not only unravel signaling pathway growth antibacterial defense, but also expand role beyond stress.