JNK suppresses tumor formation via a gene-expression program mediated by ATF2.
AffiliationDepartment of Cell Regulation, CRUK Manchester Institute, Paterson Building, University of Manchester, Manchester
MetadataShow full item record
AbstractJNK and p38 phosphorylate a diverse set of substrates and, consequently, can act in a context-dependent manner to either promote or inhibit tumor growth. Elucidating the functions of specific substrates of JNK and p38 is therefore critical for our understanding of these kinases in cancer. ATF2 is a phosphorylation-dependent transcription factor and substrate of both JNK and p38. Here, we show ATF2 suppresses tumor formation in an orthotopic model of liver cancer and cellular transformation in vitro. Furthermore, we find that suppression of tumorigenesis by JNK requires ATF2. We identify a transcriptional program activated by JNK via ATF2 and provide examples of JNK- and ATF2-dependent genes that block cellular transformation. Significantly, we also show that ATF2-dependent gene expression is frequently downregulated in human cancers, indicating that amelioration of JNK-ATF2-mediated suppression may be a common event during tumor development.
CitationJNK suppresses tumor formation via a gene-expression program mediated by ATF2. 2014, 9 (4):1361-74 Cell Rep
- The role of c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase in insulin-induced Thr69 and Thr71 phosphorylation of activating transcription factor 2.
- Authors: Baan B, van Dam H, van der Zon GC, Maassen JA, Ouwens DM
- Issue date: 2006 Aug
- Interleukin-1beta and tetradecanoylphorbol acetate-induced biosynthesis of tumor necrosis factor alpha in human hepatoma cells involves the transcription factors ATF2 and c-Jun and stress-activated protein kinases.
- Authors: Bauer I, Al Sarraj J, Vinson C, Larsen R, Thiel G
- Issue date: 2007 Jan 1
- TGF-beta-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells.
- Authors: Kim ES, Sohn YW, Moon A
- Issue date: 2007 Jul 8
- The roles of ATF2 (activating transcription factor 2) in tumorigenesis.
- Authors: Gozdecka M, Breitwieser W
- Issue date: 2012 Feb
- Retinoblastoma protein interacts with ATF2 and JNK/p38 in stimulating the transforming growth factor-beta2 promoter.
- Authors: Li H, Wicks WD
- Issue date: 2001 Oct 1