透明质酸合酶 2 的活性受二聚化和泛素化调节。
The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination.
机构信息
Ludwig Institute for Cancer Research, Uppsala University Biomedical Center, SE-75124 Uppsala, Sweden.
出版信息
J Biol Chem. 2010 Jul 30;285(31):23647-54. doi: 10.1074/jbc.M110.127050. Epub 2010 May 27.
Abstract
Hyaluronan is a component of the extracellular matrix, which affects tissue homeostasis. In this study, we investigated the regulatory mechanisms of one of the hyaluronan-synthesizing enzymes, HAS2. Ectopic expression of Flag- and 6myc-HAS2 in COS-1 cells followed by immunoprecipitation and immunoblotting revealed homodimers; after co-transfection with Flag-HAS3, also heterodimers were seen. Furthermore, the expressed HAS2 was ubiquitinated. We identified one acceptor site for ubiquitin on lysine residue 190. Mutation of this residue led to inactivation of the enzymatic activity of HAS2. Interestingly, K190R-mutated HAS2 formed dimers with wt HAS2 and quenched the activity of wt HAS2, thus demonstrating a functional role of the dimeric configuration.
摘要
透明质酸是细胞外基质的组成部分，影响组织的动态平衡。在这项研究中，我们研究了透明质酸合成酶之一 HAS2 的调控机制。Flag 和 6myc-HAS2 在 COS-1 细胞中的异位表达，随后进行免疫沉淀和免疫印迹显示同源二聚体；与 Flag-HAS3 共转染后，还观察到异源二聚体。此外，表达的 HAS2 被泛素化。我们鉴定了赖氨酸 190 上泛素的一个接受位点。该残基的突变导致 HAS2 的酶活性失活。有趣的是，K190R 突变的 HAS2 与 wt HAS2 形成二聚体，并抑制 wt HAS2 的活性，从而证明了二聚体构象的功能作用。
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