Arylsulfatase B regulates versican expression by galectin-3 and AP-1 mediated transcriptional effects.

Arylsulfatase B regulates versican expression by galectin-3 and AP-1 mediated transcriptional effects.
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DOI:
10.1038/onc.2013.483
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发表时间:
2014-11-20
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影响因子:
8
通讯作者:
--
中科院分区:
医学1区
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--
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芳基硫酸酯酶B(N-乙酰半乳糖胺-4-硫酸酯酶; ARSB)从软骨素-4-硫酸酯(C4 S)和硫酸皮肤素中除去4-硫酸酯基团,并且是其降解所需的。在人前列腺基质和上皮细胞中,当ARSB沉默时,C4 S,多功能蛋白聚糖和多功能蛋白聚糖启动子活性增加,与C4 S共免疫沉淀的半乳糖凝集素-3下降。半乳糖凝集素-3沉默抑制ARSB沉默诱导的多功能蛋白聚糖和多功能蛋白聚糖启动子的增加,这是由于对多功能蛋白聚糖启动子中AP-1结合位点的影响。这些发现首次证明了ARSB可以调节具有C4 S附件的细胞外基质蛋白聚糖表达的转录机制。此外,在ARSB沉默后,与多功能蛋白聚糖共免疫沉淀的C4 S增加,而共免疫沉淀的EGFR下降,总EGFR增加,外源性EGF诱导的细胞增殖增加,表明ARSB对重要细胞过程的深远影响。
Arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB) removes 4-sulfate groups from chondroitin-4-sulfate (C4S) and dermatan sulfate and is required for their degradation. In human prostate stromal and epithelial cells, when ARSB was silenced, C4S, versican, and versican promoter activity increased, and the galectin-3 that co-immunoprecipitated with C4S declined. Galectin-3 silencing inhibited the ARSB-silencing induced increases in versican and versican promoter, due to effects on the AP-1 binding site in the versican promoter. These findings demonstrate for the first time the transcriptional mechanism whereby ARSB can regulate expression of an extracellular matrix proteoglycan with C4S attachments. In addition, following ARSB silencing, C4S that co-immunoprecipitated with versican increased, whereas co-immunoprecipitated EGFR declined, total EGFR increased, and exogenous EGF-induced cell proliferation increased, suggesting profound effects of ARSB on vital cell processes.
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