CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne BP64182, F-31077 Toulouse, France.
PLoS One. 2012;7(8):e43798. doi: 10.1371/journal.pone.0043798. Epub 2012 Aug 20.
The ASB2α protein is the specificity subunit of an E3 ubiquitin ligase complex involved in hematopoietic differentiation and is proposed to exert its effects by regulating the turnover of specific proteins. Three ASB2α substrates have been described so far: the actin-binding protein filamins, the Mixed Lineage Leukemia protein, and the Janus kinases 2 and 3. To determine the degradation of which substrate drives ASB2α biological effects is crucial for the understanding of ASB2α functions in hematopoiesis. Here, we show that neither endogenous nor exogenously expressed ASB2α induces degradation of JAK proteins in hematopoietic cells. Furthermore, we performed molecular modeling to generate the first structural model of an E3 ubiquitin ligase complex of an ASB protein bound to one of its substrates.
ASB2α 蛋白是一种参与造血分化的 E3 泛素连接酶复合物的特异性亚基，据推测其通过调节特定蛋白质的周转率发挥作用。迄今为止，已经描述了三种 ASB2α 底物：肌动蛋白结合蛋白细丝蛋白、混合谱系白血病蛋白以及 Janus 激酶 2 和 3。确定哪种底物的降解驱动 ASB2α 的生物学效应对于理解 ASB2α 在造血中的功能至关重要。在这里，我们表明内源性或外源性表达的 ASB2α 均不会诱导造血细胞中 JAK 蛋白的降解。此外，我们进行了分子建模，生成了第一个与 ASB 蛋白及其一种底物结合的 E3 泛素连接酶复合物的结构模型。
