Common interactions between S100A4 and S100A9 defined by a novel chemical probe.

Common interactions between S100A4 and S100A9 defined by a novel chemical probe.
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DOI:
10.1371/journal.pone.0063012
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Leanderson T
Leanderson T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Björk P;Källberg E;Wellmar U;Riva M;Olsson A;He Z;Törngren M;Liberg D;Ivars F;Leanderson T

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S100A4和S100A9蛋白被认为在肿瘤生长和转移的控制中起作用。我们在这里展示了一种化学探针,氧氯胺(OX),被选择用于抑制S100A9和晚期糖基化终产物受体(RAGE)之间的相互作用,与S100A9和S100A4相互作用。此外,我们发现S100A9和S100A4与RAGE和TLR4相互作用;因此,尽管S100A4和S100A9的一级序列具有多样性,但它们具有相似的功能元件。这进一步证实了S100A4和S100A9在体外和体内都是二聚化的。所有这些相互作用都需要在细胞外空间而不是细胞内发现的Zn++水平。有趣的是,S100A4和S100A9在健康动物和患有炎症性疾病或肿瘤负担的动物中都通过不同的CD11b+亚群表达。因此,本文描述的S100A9和S100A4的功能,包括异源二聚化,可能反映了S100A9和S100A4被释放到细胞外环境中。
S100A4 and S100A9 proteins have been described as playing roles in the control of tumor growth and metastasis. We show here that a chemical probe, oxyclozanide (OX), selected for inhibiting the interaction between S100A9 and the receptor for advanced glycation end-products (RAGE) interacts with both S100A9 and S100A4. Furthermore, we show that S100A9 and S100A4 interact with RAGE and TLR4; interactions that can be inhibited by OX. Hence, S100A4 and S100A9 display similar functional elements despite their primary sequence diversity. This was further confirmed by showing that S100A4 and S100A9 dimerize both in vitro and in vivo. All of these interactions required levels of Zn++ that are found in the extracellular space but not intracellularly. Interestingly, S100A4 and S100A9 are expressed by distinct CD11b+ subpopulations both in healthy animals and in animals with either inflammatory disease or tumor burden. The functions of S100A9 and S100A4 described in this paper, including heterodimerization, may therefore reflect S100A9 and S100A4 that are released into the extra-cellular milieu.
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