Document Detail


DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stress.
MedLine Citation:
PMID:  18332104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
F Kappes; J Fahrer; M S Khodadoust; A Tabbert; C Strasser; N Mor-Vaknin; M Moreno-Villanueva; A Bürkle; D M Markovitz; E Ferrando-May
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-03-10
Journal Detail:
Title:  Molecular and cellular biology     Volume:  28     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-29     Completed Date:  2008-05-14     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3245-57     Citation Subset:  IM    
Affiliation:
University of Konstanz, Department of Biology, Box X911, D-78457 Konstanz, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal
Apoptosis / physiology*
Arthritis, Juvenile Rheumatoid / immunology
Autoantibodies / metabolism
Cell Line
Chromatin / metabolism
Chromosomal Proteins, Non-Histone / chemistry,  genetics,  immunology,  metabolism*
HeLa Cells
Humans
Jurkat Cells
Mice
Mutagens / toxicity*
Oncogene Proteins / chemistry,  genetics,  immunology,  metabolism*
Phosphorylation
Poly Adenosine Diphosphate Ribose / metabolism*
Protein Processing, Post-Translational
Recombinant Proteins / chemistry,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
T32-GM07863/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Autoantibodies; 0/Chromatin; 0/Chromosomal Proteins, Non-Histone; 0/Dek protein, human; 0/Mutagens; 0/Oncogene Proteins; 0/Recombinant Proteins; 26656-46-2/Poly Adenosine Diphosphate Ribose
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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