The Activity of Hyaluronan Synthase 2 Is Regulated by Dimerization and Ubiquitination

被引：94

作者：

Karousou, Eugenia

Kamiryo, Masaru

Skandalis, Spyros S.

Ruusala, Aino

Asteriou, Trias

Passi, Alberto ^{[2
]}

Yamashita, Hidetoshi ^{[3
]}

Hellman, Ulf ^{[1
]}

Heldin, Carl-Henrik ^{[1
]}

Heldin, Paraskevi ^{[1
]}

机构：

[1] Uppsala Univ, Biomed Ctr, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden

[2] Univ Insubria, DSBSC, I-21100 Varese, Italy

[3] Yamagata Univ, Sch Med, Dept Ophthalmol & Visual Sci, Yamagata 9909585, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 31期

关键词：

GROWTH-FACTOR; MOLECULAR-CLONING; ACTIVATION; BIOSYNTHESIS; EXPRESSION; TRANSPORT; PATHWAY;

D O I：

10.1074/jbc.M110.127050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：23647 / 23654

页数：8

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