DEK is a poly(ADP-ribose)-acceptor in apoptosis and mediates resistance to genotoxic stress

University of Konstanz, Department of Biology, Box X911, D-78457 Konstanz, Germany; Department of Internal Medicine, Division of Infectious Diseases, Program in Immunology, and Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA

^* To whom correspondence should be addressed. Email: elisa.may{at}uni-konstanz.de.

	Abstract

DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity and a major component of metazoan chromatin. The intracellular cues that control DEK's binding to DNA and its pleiotropic functions in DNA- and RNA-dependent processes have remained mainly elusive so far. Our recent finding that DEK's phosphorylation status is altered during death-receptor mediated apoptosis suggested a potential involvement of DEK in stress signaling. In this study we show that in cells committed to die, a portion of the cellular DEK pool is extensively posttranslationally modified by phosphorylation and poly(ADP-ribosyl)ation. Through interference with DEK expression, we further show that DEK promotes the repair of DNA lesions and protects cells from genotoxic agents that typically trigger Poly(ADP-ribose)polymerase activation. Postranslational modification of DEK during apoptosis is accompanied by removal of the protein from chromatin and its release into the extracellular space. Released modified DEK is recognized by autoantibodies present in the synovial fluid of JRA/JIA patients. These findings point at a crucial role of poly(ADP-ribosyl)ation in shaping DEKs autoantigenic properties and in its function as a promoter of cell survival.