DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stress.
DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity and a major component of metazoan chromatin. The intracellular cues that control the binding of DEK to DNA and its pleiotropic functions in DNA- and RNA-dependent processes have remained mainly elusive so far. Our recent finding that the phosphorylation status of DEK 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. The posttranslational modification of DEK during apoptosis is accompanied by the removal of the protein from chromatin and its release into the extracellular space. Released modified DEK is recognized by autoantibodies present in the synovial fluids of patients affected by juvenile rheumatoid arthritis/juvenile idiopathic arthritis. These findings point to a crucial role of poly(ADP-ribosyl)ation in shaping DEK's autoantigenic properties and in its function as a promoter of cell survival.
Kappes
F
F
University of Konstanz, Department of Biology, Box X911, D-78457 Konstanz, Germany.
Fahrer
J
J
Khodadoust
M S
MS
Tabbert
A
A
Strasser
C
C
Mor-Vaknin
N
N
Moreno-Villanueva
M
M
Bürkle
A
A
Markovitz
D M
DM
Ferrando-May
E
E
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D001171:Arthritis, Juvenile / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D009153:Mutagens; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011994:Recombinant Proteins; D011064:Poly Adenosine Diphosphate Ribose