Identification of poly(ADP-ribose) polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression
2006 (English)In: BMC Molecular Biology, ISSN 1471-2199, Vol. 7Article in journal (Refereed) Published
Background: S100 proteins, a multigenic family of non-ubiquitous cytoplasmic Ca2+-binding proteins, have been linked to human pathologies in recent years. Dysregulated expression of S100 proteins, including S100A9, has been reported in the epidermis as a response to stress and in association with neoplastic disorders. Recently, we characterized a regulatory element within the S100A9 promotor, referred to as MRE that drives the S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner (Kerkhoff et al. ( 2002) J. Biol. Chem. 277, 41879-41887). Results: 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-I (PARP-I) 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-l with 1,5- isoquinolinediol (DiQ). Conclusion: The candidates, poly(ADP-ribose) polymerase-l (PARP-l) 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.
Place, publisher, year, edition, pages
2006. Vol. 7
activation, breast-cancer cells, c/ebp-alpha, calcium-binding proteins, dna-damage, epidermal differentiation, prostate-cancer, psoriasis, skin carcinogenesis, squamous-cell carcinoma
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:liu:diva-86974DOI: 10.1186/1471-2199-7-48ISI: 000243516200001OAI: oai:DiVA.org:liu-86974DiVA: diva2:583957