Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression.
Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression.
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将聚（ADP-核糖）聚合酶-1和KU70/KU80鉴定为S100A9基因表达的转录调节剂。
DOI：
10.1186/1471-2199-7-48
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发表时间：
2006-12-22
影响因子：
--
通讯作者：
Kerkhoff, Claus
中科院分区：
文献类型：
--
作者：
Grote, Jens;Koenig, Simone;Ackermann, Doreen;Sopalla, Claudia;Benedyk, Malgorzata;Los, Marek;Kerkhoff, Claus
S100蛋白是一个非普遍存在的胞浆内钙结合蛋白的多基因家族，近年来被认为与人类的病理有关。S100蛋白的异常表达，包括S100A9，已被报道在表皮中作为对应激的反应并与肿瘤疾病相关。最近，我们鉴定了S100A9启动子中的一个调节元件，称为MRE，它以细胞类型特异的、激活和分化依赖的方式驱动S100A9基因的表达(Kerkhoff等人)。(2002)J.Biol.化学。277、41879-41887)。在本研究中，我们研究了与MRE结合的转录因子。利用MRE基序进行下拉分析，用质谱仪鉴定了聚ADP-核糖聚合酶-1(PARP-1)和异二聚体复合体Ku70/Ku80，并用染色质免疫沉淀对其进行了确认。1，5-异喹啉二醇(DIQ)抑制PARP-1后，TPA诱导的HaCaT角质形成细胞S100A9基因表达被阻断。这些候选基因，聚(ADP-核糖)聚合酶-1(PARP-1)和异二聚体复合体Ku70/Ku80，已知参与了炎症性疾病和肿瘤的发生。后者可能表明S100和炎症相关癌症之间可能存在联系。
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). 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.
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影响因子：
4.4
作者：
Henkel, GW;McKercher, SR;Maki, RA
通讯作者：
Maki, RA
DOI：
10.1007/s00432-004-0555-x
发表时间：
2004-08-01
影响因子：
3.6
作者：
Ji, JF;Zhao, LQ;Liu, ZH
通讯作者：
Liu, ZH
影响因子：
14.9
作者：
Kannan, P;Yu, YH;Tainsky, MA
通讯作者：
Tainsky, MA
影响因子：
4.8
作者：
Kerkhoff, C;Hofmann, HA;Klempt, M
通讯作者：
Klempt, M
影响因子：
11.2
作者：
Kennedy, RD;Gorski, JJ;Harkin, DP
通讯作者：
Harkin, DP