Hoer Simon, Smith Lorraine, Lehner Paul J
Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
FEBS Lett. 2007 Jan 9;581(1):45-51. doi: 10.1016/j.febslet.2006.11.075. Epub 2006 Dec 8.
The membrane associated RING-CH (MARCH) family of genes encode a novel group of RING-type ubiquitin E3 ligases. Overexpression of one of these family members, MARCH-IX, leads to a downregulation of cell surface major histocompatibility complex (MHC) class I and CD4. Here, we identify MARCH-IX as the first ubiquitin E3 ligase to control expression of the critical cell adhesion molecule ICAM-1. MARCH-IX expression causes ubiquitination and downregulation of ICAM-1 and a short alternative transcript of MARCH-IX lacking the RING-CH domain, termed MARCH-IX RINGless, is shown to act as a positive regulator of MARCH-IX activity.
膜相关的RING-CH(MARCH)基因家族编码一类新型的RING型泛素E3连接酶。这些家族成员之一MARCH-IX的过表达会导致细胞表面主要组织相容性复合体(MHC)I类分子和CD4的下调。在此,我们确定MARCH-IX是首个控制关键细胞黏附分子细胞间黏附分子-1(ICAM-1)表达的泛素E3连接酶。MARCH-IX的表达导致ICAM-1的泛素化和下调,并且缺少RING-CH结构域的MARCH-IX短替代转录本(称为无RING结构域的MARCH-IX)被证明可作为MARCH-IX活性的正调节因子。