Lin Lan, Nemeth Elizabeta, Goodnough Julia B, Thapa Dharma R, Gabayan Victoria, Ganz Tomas
Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Blood Cells Mol Dis. 2008 Jan-Feb;40(1):122-31. doi: 10.1016/j.bcmd.2007.06.023. Epub 2007 Sep 14.
As the principal iron-regulatory hormone, hepcidin plays an important role in systemic iron homeostasis. The regulation of hepcidin expression by iron loading appears to be unexpectedly complex and has attracted much interest. The GPI-linked membrane protein hemojuvelin (GPI-hemojuvelin) is an essential upstream regulator of hepcidin expression. A soluble form of hemojuvelin (s-hemojuvelin) exists in blood and acts as antagonist of GPI-hemojuvelin to downregulate hepcidin expression. The release of s-hemojuvelin is negatively regulated by both transferrin-bound iron (holo-Tf) and non-transferrin-bound iron (FAC), indicating s-hemojuvelin could be one of the mediators of hepcidin regulation by iron. In this report, we investigate the proteinase involved in the release of s-hemojuvelin and show that s-hemojuvelin is released by a proprotein convertase through the cleavage at a conserved polybasic RNRR site.
作为主要的铁调节激素，铁调素在全身铁稳态中发挥着重要作用。铁负荷对铁调素表达的调节似乎出人意料地复杂，引起了广泛关注。糖基磷脂酰肌醇连接的膜蛋白血色素沉着症相关蛋白（GPI-血色素沉着症相关蛋白）是铁调素表达必不可少的上游调节因子。血色素沉着症相关蛋白的一种可溶性形式（s-血色素沉着症相关蛋白）存在于血液中，作为GPI-血色素沉着症相关蛋白的拮抗剂下调铁调素的表达。s-血色素沉着症相关蛋白的释放受到转铁蛋白结合铁（全铁转铁蛋白）和非转铁蛋白结合铁（FAC）的负调节，表明s-血色素沉着症相关蛋白可能是铁调节铁调素的介质之一。在本报告中，我们研究了参与s-血色素沉着症相关蛋白释放的蛋白酶，并表明s-血色素沉着症相关蛋白是由一种前蛋白转化酶通过在保守的多碱性RNRR位点切割而释放的。
