Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, PO Box 21, Haartmaninkatu 3, FI-00014 Helsinki, Finland.
Biochem Biophys Res Commun. 2012 May 4;421(2):274-9. doi: 10.1016/j.bbrc.2012.03.151. Epub 2012 Apr 6.
Stanniocalcin 2 (STC2) is a homolog of stanniocalcin 1, a 56kD glycoprotein hormone that originally was found to confer calcitonin-like activity in fish. Human STC2 is expressed in various tissues such as kidney, spleen, heart, and pancreas. STC2 has been demonstrated to be induced by different kinds of stress and display cytoprotective activity, but the molecular mechanism is poorly understood. Heme oxygenase 1 (HO1) degrades heme to biliverdin, carbon monoxide and free iron, and is a stress-responsive protein. Using yeast two-hybrid screening we identified HO1 as a binding partner of STC2. The interaction was validated by in vivo co-immunoprecipitation and immunofluorescence. The binding site for HO1 was located to amino acids 181-200 of STC2. We also found that STC2 binds hemin via a consensus heme regulatory motif. Moreover, STC2 expression was induced by heat shock in HEK293 cells. Taken together, our findings point to three novel functions of STC2, and suggest that STC2 interacts with HO1 to form a eukaryotic 'stressosome' involved in the degradation of heme.
钙结合蛋白 2（STC2）是钙结合蛋白 1 的同源物，钙结合蛋白 1 最初被发现具有鱼类降钙素样活性的 56kD 糖蛋白激素。人类 STC2 在各种组织中表达，如肾脏、脾脏、心脏和胰腺。STC2 已被证明可被不同类型的应激诱导，并具有细胞保护活性，但分子机制尚不清楚。血红素加氧酶 1（HO1）将血红素降解为胆绿素、一氧化碳和游离铁，是一种应激反应蛋白。我们使用酵母双杂交筛选鉴定出 HO1 是 STC2 的结合伴侣。通过体内共免疫沉淀和免疫荧光验证了相互作用。HO1 的结合位点位于 STC2 的 181-200 个氨基酸。我们还发现 STC2 通过血红素调节基序结合血红素。此外，STC2 在 HEK293 细胞中受到热休克的诱导。总之，我们的研究结果表明 STC2 具有三个新的功能，并提示 STC2 与 HO1 相互作用形成参与血红素降解的真核“应激体”。
