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FEBS Lett. 2007 Jan 9;581(1):45-51. Epub 2006 Dec 8.

MARCH-IX mediates ubiquitination and downregulation of ICAM-1.

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  • 1Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK.


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.

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