%0 Journal Article
%T Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression
%A Jens Grote
%A Simone K£¿nig
%A Doreen Ackermann
%A Claudia Sopalla
%A Malgorzata Benedyk
%A Marek Los
%A Claus Kerkhoff
%J BMC Molecular Biology
%D 2006
%I BioMed Central
%R 10.1186/1471-2199-7-48
%X In the present study, we investigated transcription factors that bind to MRE. Using the MRE motif for a pull-down assay, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80 were identified by mass spectrometry and confirmed by chromatin immunoprecipitation. Furthermore, TPA-induced S100A9 gene expression in HaCaT keratinocytes was blocked after the pharmacologic inhibition of PARP-1 with 1,5-isoquinolinediol (DiQ).The candidates, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80, are known to participate in inflammatory disorders as well as tumorgenesis. The latter may indicate a possible link between S100 and inflammation-associated cancer.Members of the S100 protein family comprise a multigenic group of non-ubiquitous cytoplasmic Ca2+-binding proteins of the EF-hand type, differentially expressed in a wide variety of cell types. In particular, S100A8 and S100A9 also known as calgranulins are abundant in myeloid cells. The expression of S100A8 and S100A9 is increased in various disorders, such as rheumatoid arthritis, inflammatory bowel disease and vasculitis [1]. The S100/calgranulins are associated with inflammatory disorders as they are secreted from phagocytes upon cellular activation [2,3], and track disease activity. In addition to their abundance in myeloid cells, S100A8 and S100A9 can also be found in the epidermis as a response to stress. For example, they are significantly up-regulated in differentiating suprabasal wound keratinocytes [4,5], in response to UVB irradiation [6], and in psoriasis keratinocytes [7], suggesting a role for these proteins in the pathogenesis of certain diseases. Based on these findings, the two S100 proteins have been referred to as stress-regulated proteins [8].An additional important indication for their involvement in inflammatory and neoplastic disorders is that most S100 genes are found near a region on human chromosome 1q21 which is responsible for a number of chromosom
%U http://www.biomedcentral.com/1471-2199/7/48